Daubert, D. M., Kelley, J. L., Udod, Y. G., Habor, C., Kleist, C. G., Furman, I. K., et al. (2016). Human enamel thickness and ENAM polymorphism. *Int. J. Oral Sci.* 8, 93–97. doi:10.1038/ijos.2016.1

de La Dure-Molla, M., Fournier, B. P., Manzanares, M. C., Acevedo, A. C., Hennekam, R. C., Friedlander, L., et al. (2019). Elements of morphology: Standard terminology for the teeth and classifying genetic dental disorders. *Am. J. Med. Genet.* A 179, 1913–1981. doi:10.1002/ajmg.a.61316

de la Dure-Molla, M., Quentric, M., Yamaguti, P. M., Acevedo, A.-C., Mighell, A. J., Vikkula, M., et al. (2014). Pathognomonic oral profile of Enamel Renal Syndrome (ERS) caused by recessive FAM20A mutations. *Orphanet J. Rare Dis.* 9, 84. doi:10.1186/1750-1172-9-84

Deidrick, K. K. M., Early, M., Constance, J., Stein, M., and Fete, T. J. (2016). Cognitive and psychological functioning in focal dermal hypoplasia. *Am. J. Med. Genet. C Semin. Med. Genet.* 172, 34–40. doi:10.1002/ajmg.c.31471

Dellow, E. L., Harley, K. E., Unwin, R. J., Wrong, O., Winter, G. B., and Parkins, B. J. (1998). Amelogenesis imperfecta, nephrocalcinosis, and hypocalciuria syndrome in two siblings from a large family with consanguineous parents. *Nephrol. Dial. Transpl.* 13 (12), 3193–3196. doi:10.1093/ndt/13.12.3193

DePristo, M. A., Banks, E., Poplin, R., Garimella, K. V., Maguire, J. R., Hartl, C., et al. (2011). A framework for variation discovery and genotyping using next-generation DNA sequencing data. *Nat. Genet.* 43, 491–498. doi:10.1038/ng.806

Dong, J., Amor, D., Aldred, M. J., Gu, T., Escamilla, M., and MacDougall, M. (2005). DLX3 mutation associated with autosomal dominant amelogenesis imperfecta with taurodontism. *Am. J. Med. Genet.* A 133A, 138–141. doi:10.1002/ajmg.a.30521

Dourado, M. R., Dos Santos, C. R. R., Dumitriu, S., Iancu, D., Albanyan, S., Kleta, R., et al. (2019). Enamel renal syndrome: A novel homozygous FAM20A founder mutation in 5 new Brazilian families. *Eur. J. Med. Genet.* 62 (11), 103561. doi:10.1016/j.ejmg.2018.10.013

Dubail, J., Huber, C., Chantepie, S., Sonntag, S., Tüysüz, B., Mihci, E., et al. (2018). SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects. *Nat. Commun.* 9, 3087. doi:10.1038/s41467-018-05191-8

Dugan, S. L., Temme, R. T., Olson, R. A., Mikhailov, A., Law, R., Mahmood, H., et al. (2015). New recessive truncating mutation in LTBP3 in a family with oligodontia, short stature, and mitral valve prolapse. *Am. J. Med. Genet.* A 167, 1396–1399. doi:10.1002/ajhg.a.37049

Durmaz, C. D., McGrath, J., Liu, L., and Karabulut, H. G. (2018). A novel PORCN frameshift mutation leading to focal dermal hypoplasia: A case report. *Cytogenet Genome Res.* 154, 119–121. doi:10.1159/000487580

Duverger, O., Ohara, T., Bible, P. W., Zah, A., and Morasso, M. I. (2017). DLX3-Dependent regulation of ion transporters and carbonic anhydrases is crucial for enamel mineralization. *J. Bone Min. Res.* 32, 641–653. doi:10.1002/jbmr.3022

El-Sayed, W., Parry, D. A., Shore, R. C., Ahmed, M., Jafri, H., Rashid, Y., et al. (2009). Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta. *Am. J. Hum. Genet.* 85, 699–705. doi:10.1016/j.ajhg.2009.09.014

Exome Aggregation ConsortiumLek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., et al. (2016). Analysis of protein-coding genetic variation in 60,706 humans. *Nature* 536, 285–291. doi:10.1038/nature19057

Feldmeyer, L., Huber, M., Fellmann, F., Beckmann, J. S., Frenk, E., and Hohl, D. (2006). Confirmation of the origin of NISCH syndrome. *Hum. Mutat.* 27, 408–410. doi:10.1002/humu.20333

Feske, S., Müller, J. M., Graf, D., Kroczek, R. A., Dräger, R., Niemeyer, C., et al. (1996). Severe combined immunodeficiency due to defective binding of the nuclear factor of activated T cells in T lymphocytes of two male siblings. *Eur. J. Immunol.* 26 (9), 2119–2126. doi:10.1002/eji.1830260924

Feske, S. (2010). CRAC channelopathies. *Pflugers Arch.* 460, 417–435. doi:10.1007/s00424-009-0777-5

Flores, E. R., Tsai, K. Y., Crowley, D., Sengupta, S., Yang, A., McKeon, F., et al. (2002). p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. *Nature* 416, 560–564. doi:10.1038/416560a

Fouillen, A., Dos Santos Neves, J., Mary, C., Castonguay, J.-D., Moffatt, P., Baron, C., et al. (2017). Interactions of AMTN, ODAM and SCPPPPQ1 proteins of a specialized basal lamina that attaches epithelial cells to tooth mineral. *Sci. Rep.* 7, 46683. doi:10.1038/srep46683

Frick, K. K., Krieger, N. S., Nehrke, K., and Bushinsky, D. A. (2009). Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. *J. Bone Min. Res.* 24, 305–313. doi:10.1359/jbmr.081015

Frisk, S., Grandpeix-Guyodo, C., Popovic Silverfeldt, K., Hjartarson, H. T., Chatzianastassiou, D., Magnusson, I., et al. (2018). Goltz syndrome in males: A clinical report of a male patient carrying a novel PORCN variant and a review of the literature. *Clin. Case Rep.* 6, 2103–2110. doi:10.1002/ccr3.1783

Furukawa, Y., Haruyama, N., Nikaido, M., Nakanishi, M., Ryu, N., Oh-Hora, M., et al. (2017). Stim1 regulates enamel mineralization and ameloblast modulation. *J. Dent. Res.* 96, 1422–1429. doi:10.1177/0022034517719872

Gasse, B., Karayigit, E., Mathieu, E., Jung, S., Garret, A., Huckert, M., et al. (2013). Homozygous and compound heterozygous MMP20 mutations in amelogenesis imperfecta. *J. Dent. Res.* 92, 598–603. doi:10.1177/0022034513488393

Gasse, B., Prasad, M., Delgado, S., Huckert, M., Kawczynski, M., Garret-Bernardin, A., et al. (2017). Evolutionary analysis predicts sensitive positions of MMP20 and validates

newly- and previously-identified MMP20 mutations causing amelogenesis imperfecta. *Front. Physiol.* 8, 398. doi:10.3389/fphys.2017.00398

Geoffroy, V., Herenger, Y., Kress, A., Stoetzel, C., Piton, A., Dollfus, H., et al. (2018). AnnotSV: An integrated tool for structural variations annotation. *Bioinformatics* 34, 3572–3574. doi:10.1093/bioinformatics/bty304

Geoffroy, V., Pizot, C., Redin, C., Piton, A., Vasli, N., Stoetzel, C., et al. (2015). VaRank: A simple and powerful tool for ranking genetic variants. *PeerJ* 3, e796. doi:10.7717/peerj.796

Gibson, C. W., Yuan, Z. A., Hall, B., Longenecker, G., Chen, E., Thyagarajan, T., et al. (2001). Amelogenin-deficient mice display an amelogenesis imperfecta phenotype. *J. Biol. Chem.* 276, 31871–31875. doi:10.1074/jbc.M104624200

Goodwin, A. F., Tidyman, W. E., Jheon, A. H., Sharir, A., Zheng, X., Charles, C., et al. (2014). Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. *Hum. Mol. Genet.* 23, 682–692. doi:10.1093/hmg/ddt455

Greene, S. R., Yuan, Z. A., Wright, J. T., Amjad, H., Abrams, W. R., Buchanan, J. A., et al. (2002). A new frameshift mutation encoding a truncated amelogenin leads to X-linked amelogenesis imperfecta. *Arch. Oral Biol.* 47, 211–217. doi:10.1016/s0003-9969(01)00111-x

Guerrini, R., Mei, D., Kerti-Szigeti, K., Pepe, S., Koenig, M. K., Von Allmen, G., et al. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. *Brain* 145, 2687–2703. doi:10.1093/brain/awac145

Guo, D., Ling, J., Wang, M.-H., She, J.-X., Gu, J., and Wang, C.-Y. (2005). Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis. *Mol. Pain* 1, 15–8069. doi:10.1186/1744-8069-1-15

Guo, D., Regalado, E. S., Pinard, A., Chen, J., Lee, K., Rigelsky, C., et al. (2018). LTBP3 pathogenic variants predispose individuals to thoracic aortic aneurysms and dissections. *Am. J. Hum. Genet.* 102, 706–712. doi:10.1016/j.ajhg.2018.03.002

Happle, R., and Lenz, W. (1977). Striation of bones in focal dermal hypoplasia: Manifestation of functional mosaicism? *Br. J. Dermatol* 96, 133–135. doi:10.1111/j.1365-2133.1977.tb12534.x

Hardies, K., de Kovel, C. G. F., Weckhuysen, S., Asselbergh, B., Geuens, T., Deconinck, T., et al. (2015). Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. *Brain* 138, 3238–3250. doi:10.1093/brain/awv263

Harrison, S. M., Biesecker, L. G., and Rehm, H. L. (2019). Overview of specifications to the the ACMG/AMP variant interpretation guidelines. *Curr. Protoc. Hum. Genet.* 103, e93. doi:10.1002/cphg.93

Hart, P. S., Aldred, M. J., Crawford, P. J. M., Wright, N. J., Hart, T. C., and Wright, J. T. (2002a). Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations. *Arch. Oral Biol.* 47, 261–265. doi:10.1016/s0003-9969(02)00003-1

Hart, P. S., Hart, T. C., Michalec, M. D., Ryu, O. H., Simmons, D., Hong, S., et al. (2004). Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. *J. Med. Genet.* 41, 545–549. doi:10.1136/jmg.2003.017657

Hart, P. S., Hart, T. C., Simmer, J. P., and Wright, J. T. (2002b). A nomenclature for X-linked amelogenesis imperfecta. *Arch. Oral Biol.* 47, 255–260. doi:10.1016/s0003-9969(02)00005-5

Hart, T. C., Hart, P. S., Gorry, M. C., Michalec, M. D., Ryu, O. H., Uygur, C., et al. (2003). Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects. *J. Med. Genet.* 40 (12), 900–906. doi:10.1136/jmg.40.12.900

Harutunian, K., Figueiredo, R., and Gay-Escoda, C. (2011). Tuberous sclerosis complex with oral manifestations: A case report and literature review. *Med. Oral Patol. Oral Cir. Bucal* 16, e478–e481. doi:10.4317/medoral.16.e478

Hassan, M. Q., Javed, A., Morasso, M. I., Karlin, J., Montecino, M., Wijnen, A. J. van, et al. (2004). Dlx3 transcriptional regulation of osteoblast differentiation: Temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene. *Mol. Cell. Biol.* 24, 9248–9261. doi:10.1128/MCB.24.20.9248-9261.2004

Heimler, A., Fox, J. E., Hershey, J. E., and Crespi, P. (1991). Sensorineural hearing loss, enamel hypoplasia, and nail abnormalities in sibs. *Am. J. Med. Genet.* 39, 192–195. doi:10.1002/ajmg.1320390214

Holcroft, J., and Ganss, B. (2011). Identification of amelotin- and ODAM-interacting enamel matrix proteins using the yeast two-hybrid system. *Eur. J. Oral Sci.* 119 (1), 301–306. doi:10.1111/j.1600-0722.2011.00870.x

Hollister, D. W., Klein, S. H., De Jager, H. J., Lachman, R. S., and Rimoin, D. L. (1973). The lacrimo-auriculo-dento-digital syndrome. *J. Pediatr.* 83, 438–444. doi:10.1016/s0022-3476(73)80268-9

Hu, J. C.-C., Chan, H.-C., Simmer, S. G., Seymen, F., Richardson, A. S., Hu, Y., et al. (2012a). Amelogenesis imperfecta in two families with defined AMELX deletions in ARHGAP6. *PLoS One* 7, e52052. doi:10.1371/journal.pone.0052052

Hu, J. C.-C., and Yamakoshi, Y. (2003). Enamelin and autosomal-dominant amelogenesis imperfecta. *Crit. Rev. Oral Biol. Med.* 14, 387–398. doi:10.1177/154411130301400602

Hu, P., Lacruz, R. S., Smith, C. E., Smith, S. M., Kurtz, I., and Paine, M. L. (2012b). Expression of the sodium/calcium/potassium exchanger, NCKX4, in ameloblasts. *Cells Tissues Organs* 196, 501–509. doi:10.1159/000337493
Huckert, M., Mecili, H., Laugel-Haushalter, V., Stoetzel, C., Muller, J., Flori, E., et al. (2014). A novel mutation in the ROGDI gene in a patient with kohtschütter-tönz syndrome. *Mol. Syndromol.* 5, 293–298. doi:10.1159/000366252

Huckert, M., Stoetzel, C., Morkmued, S., Laugel-Haushalter, V., Geoffroy, V., Muller, J., et al. (2015). Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta. *Hum. Mol. Genet.* 24, 3038–3049. doi:10.1093/hmg/ddv053

Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K.-L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. *Nat. Cell. Biol.* 4, 648–657. doi:10.1038/ncb839

Inoue, K., Zhuang, L., and Ganapathy, V. (2002). Human Na⁺-coupled citrate transporter: Primary structure, genomic organization, and transport function. *Biochem. Biophys. Res. Commun.* 299, 465–471. doi:10.1016/S0006-291X(02)02669-4

Intarak, N., Theerapanon, T., Thaweesappithak, S., Suphapeetiporn, K., Pontaveetus, T., and Shotelersuk, V. (2019). Genotype-phenotype correlation and expansion of orodental anomalies in LTBP3-related disorders. *Mol. Genet. Genomics* 294, 773–787. doi:10.1007/s00438-019-01547-x

Iwase, M., Kaneko, S., Kim, H., Satta, Y., and Takahata, N. (2007). Evolutionary history of sex-linked mammalian amelogenin genes. *Cells Tissues Organs* 186, 49–59. doi:10.1159/000102680

Jabs, E. W., Müller, U., Li, X., Ma, L., Luo, W., Haworth, I. S., et al. (1993). A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. *Cell* 75, 443–450. doi:10.1016/0092-8674(93)90379-5

Jagtap, R., Alansari, R., Ruprecht, A., and Kashtwari, D. (2019). Trichodentooskeletal syndrome: A case report and review of literature. *BJR Case Rep.* 5, 20190039. doi:10.1259/bjcr.20190039

Jain, P., Kaul, R., Saha, S., and Sarkar, S. (2017). Tricho-dento-oskeletal syndrome and precocious eruption. *J. Clin. Exp. Dent.* 9, e494–e497. doi:10.4317/jced.53348

Jalili, I. K., and Smith, N. J. (1988). A progressive cone-rod dystrophy and amelogenesis imperfecta: A new syndrome. *J. Med. Genet.* 25, 738–740. doi:10.1136/jmg.25.11.738

Jani, P., Nguyen, Q. C., Almpani, K., Keyvanfar, C., Mishra, R., Liberton, D., et al. (2020). Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation. *J. Med. Genet.* 57, 699–707. doi:10.1136/jmedgenet-2019-106678

Jaureguiberry, G., De la Dure-Molla, M., Parry, D., Quentric, M., Himmerkus, N., Koike, T., et al. (2012). Nephrocalcinosis (enamel renal syndrome) caused by autosomal recessive FAM20A mutations. *Nephron Physiol.* 122, 1–6. doi:10.1159/000349989

Ji, Y., Li, C., Tian, Y., Gao, Y., Dong, Z., Xiang, L., et al. (2021). Maturation stage enamel defects in Odontogenesis-associated phosphoprotein (Odaph) deficient mice. *Dev. Dyn.* 250, 1505–1517. doi:10.1002/dvdy.336

Kantaputra, P. N., Hamada, T., Kumchai, T., and McGrath, J. A. (2003). Heterozygous mutation in the SAM domain of p63 underlies rapp-hodgkin ectodermal dysplasia. *J. Dent. Res.* 82, 433–437. doi:10.1177/154405910308200606

Katsura, K. A., Horst, J. A., Chandra, D., Le, T. Q., Nakano, Y., Zhang, Y., et al. (2014). WDR72 models of structure and function: A stage-specific regulator of enamel mineralization. *Matrix Biol.* 38, 48–58. doi:10.1016/j.matbio.2014.06.005

Katsura, K., Nakano, Y., Zhang, Y., Shemirani, R., Li, W., and Den Besten, P. (2022). WDR72 regulates vesicle trafficking in ameloblasts. *Sci. Rep.* 12, 2820. doi:10.1038/s41598-022-06751-1

Kausalya, P. J., Amasheh, S., Günzel, D., Wurps, H., Müller, D., Fromm, M., et al. (2006). Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of Claudin-16. *J. Clin. Invest.* 116, 878–891. doi:10.1172/JCI26323

Khandelwal, P., Maheshnull, V., Mathur, V. P., Raut, S., Geetha, T. S., Nair, S., et al. (2021). Phenotypic variability in distal acidification defects associated with WDR72 mutations. *Pediatr. Nephrol.* 36, 881–887. doi:10.1007/s00467-020-04747-5

Kim, J.-W., Lee, S.-K., Lee, Z. H., Park, J.-C., Lee, K.-E., Lee, M.-H., et al. (2008). FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. *Am. J. Hum. Genet.* 82, 489–494. doi:10.1016/j.ajhg.2007.09.020

Kim, J.-W., Seymen, F., Lin, B. P.-J., Kiziltan, B., Gencay, K., Simmer, J. P., et al. (2005a). ENAM mutations in autosomal-dominant amelogenesis imperfecta. *J. Dent. Res.* 84, 278–282. doi:10.1177/154405910508400314

Kim, J.-W., Simmer, J. P., Hart, T. C., Hart, P. S., Ramaswami, M. D., Bartlett, J. D., et al. (2005b). MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. *J. Med. Genet.* 42, 271–275. doi:10.1136/jmg.2004.024505

Kim, J.-W., Zhang, H., Seymen, F., Koruyucu, M., Hu, Y., Kang, J., et al. (2019). Mutations in RELT cause autosomal recessive amelogenesis imperfecta. *Clin. Genet.* 95, 375–383. doi:10.1111/cge.13487

Kim, J. W., Simmer, J. P., Hu, Y. Y., Lin, B. P., Boyd, C., Wright, J. T., et al. (2004). Amelogenin p.M1T and p.W4S mutations underlying hypoplastic X-linked amelogenesis imperfecta. *J. Dent. Res.* 83 (5), 378–383. doi:10.1177/154405910408300505

Kim, Y. J., Abe, Y., Kim, Y.-J., Fujiki, Y., and Kim, J.-W. (2021a). Identification of a homozygous PEX26 mutation in a heimler syndrome patient. *Genes. (Basel)* 12, 646. doi:10.3390/genes12050646

Kim, Y. J., Kang, J., Seymen, F., Koruyucu, M., Gencay, K., Shin, T. J., et al. (2017). Analyses of MMP20 missense mutations in two families with hypomaturation amelogenesis imperfecta. *Front. Physiol.* 8, 229. doi:10.3389/fphys.2017.00229

Kim, Y. J., Kang, J., Seymen, F., Koruyucu, M., Zhang, H., Kasimoglu, Y., et al. (2020). Alteration of exon definition causes amelogenesis imperfecta. *J. Dent. Res.* 99, 410–418. doi:10.1177/0022034520901708

Kim, Y. J., Lee, Y., Zhang, H., Song, J.-S., Hu, J. C.-C., Simmer, J. P., et al. (2021b). A novel de novo SP6 mutation causes severe hypoplastic amelogenesis imperfecta. *Genes. (Basel)* 12, 346. doi:10.3390/genes12030346

Kindelan, S. A., Brook, A. H., Gangemi, L., Lench, N., Wong, F. S., Fearne, J., et al. (2000). Detection of a novel mutation in X-linked amelogenesis imperfecta. *J. Dent. Res.* 79, 1978–1982. doi:10.1177/00220345000790120901

Kiritsi, D., Huilaja, L., Franzke, C.-W., Kokkonen, N., Pazzagli, C., Schwieger-Briel, A., et al. (2015). Junctional epidermolysis bullosa with LAMB3 splice-site mutations. *Acta Derm. Venereol.* 95, 849–851. doi:10.2340/00015555-2073

Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A.-K., Drechsel, D., et al. (2004). An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. *Nature* 432, 1036–1040. doi:10.1038/nature03159

Kohlschütter, A., Chappuis, D., Meier, C., Tönz, O., Vassella, F., Herschkowitz, N., et al. (1974). Familial epilepsy and yellow teeth-a disease of the CNS associated with enamel hypoplasia. *Helv. Paediatr. Acta* 29, 283–294.

Konrad, M., Schaller, A., Seelow, D., Pandey, A. V., Waldegger, S., Lesslauer, A., et al. (2006). Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement. *Am. J. Hum. Genet.* 79, 949–957. doi:10.1086/508617

Kosaki, R., Naito, Y., Torii, C., Takahashi, T., Nakajima, T., and Kosaki, K. (2008). Split hand foot malformation with whorl-like pigmentary pattern: Phenotypic expression of somatic mosaicism for the p63 mutation. *Am. J. Med. Genet. A* 146A, 2574–2577. doi:10.1002/ajmg.a.32415

Kuga, T., Sasaki, M., Mikami, T., Miane, Y., Adachi, J., Shimizu, M., et al. (2016). FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes. *Sci. Rep.* 6, 26557. doi:10.1038/srep26557

Lacruz, R. S., and Feske, S. (2015). Diseases caused by mutations in ORAI1 and STIM1. *Ann. N. Y. Acad. Sci.* 1356, 45–79. doi:10.1111/nyas.12938

Lagerström, M., Dahl, N., Iselius, L., Bäckman, B., and Pettersson, U. (1990). Mapping of the gene for X-linked amelogenesis imperfecta by linkage analysis. *Am. J. Hum. Genet.* 46, 120–125.

Lagerström, M., Dahl, N., Nakahori, Y., Nakagome, Y., Bäckman, B., Landegren, U., et al. (1991). A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1). *Genomics* 10, 971–975. doi:10.1016/0888-7543(91)90187-j

Landrum, M. J., Lee, J. M., Benson, M., Brown, G. R., Chao, C., Chitipiralla, S., et al. (2018). ClinVar: Improving access to variant interpretations and supporting evidence. *Nucleic Acids Res.* 46 (D1), D1062–D1067. doi:10.1093/nar/gkx1153

Larrégue, M., and Duterque, M. (1975). Letter: Striated osteopathy in focal dermal hypoplasia. *Arch. Dermatol* 111 (10), 1365. doi:10.1001/archderm.1975.01630220129019

Lau, E. C., Mohandas, T. K., Shapiro, L. J., Slavkin, H. C., and Snead, M. L. (1989). Human and mouse amelogenin gene loci are on the sex chromosomes. *Genomics* 4, 162–168. doi:10.1016/0888-7543(89)90295-4

Laugel-Haushalter, V., Bär, S., Schaefer, E., Stoetzel, C., Geoffroy, V., Alembik, Y., et al. (2019). A new SLC10A7 homozygous missense mutation responsible for a milder phenotype of skeletal dysplasia with amelogenesis imperfecta. *Front. Genet.* 10, 504. doi:10.3389/fgene.2019.000504

Lee, K.-E., Ko, J., Le, C. G. T., Shin, T. J., Hyun, H.-K., Lee, S.-H., et al. (2015). Novel LAMB3 mutations cause non-syndromic amelogenesis imperfecta with variable expressivity. *Clin. Genet.* 87, 90–92. doi:10.1111/cge.12340

Lee, N. P. Y., Tong, M. K., Leung, P. P., Chan, V. W., Leung, S., Tam, P.-C., et al. (2006). Kidney claudin-19: Localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease. *FEBS Lett.* 580, 923–931. doi:10.1016/j.feb.2006.01.019

Lee, S.-K., Seymen, F., Kang, H.-Y., Lee, K.-E., Gencay, K., Tuna, B., et al. (2010). MMP20 hemopexin domain mutation in amelogenesis imperfecta. *J. Dent. Res.* 89, 46–50. doi:10.1177/0022034509352844

Lee, S. K., Lee, K. E., Jeong, T. S., Hwang, Y. H., Kim, S., Hu, J. C., et al. (2011). FAM83H mutations cause ADHCA1 and alter intracellular protein localization. *J. Dent. Res.* 90 (3), 377–381. doi:10.1177/0022034510389177

Lench, N. J., and Winter, G. B. (1995). Characterisation of molecular defects in X-linked amelogenesis imperfecta (AIH1). *Hum. Mutat.* 5, 251–259. doi:10.1002/humu.1380050310

Li, X., Yin, W., Pérez-Jurado, L., Bonadio, J., and Francke, U. (1995). Mapping of human and murine genes for latent TGF-β binding protein-2 (LTBP2). *Mamm. Genome* 6, 42–45. doi:10.1007/BF00350892

Liang, T., Hu, Y., Smith, C. E., Richardson, A. S., Zhang, H., Yang, J., et al. (2019). AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-
NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. *Mol. Genet. Genomic Med.* 7, e929. doi:10.1002/mgg3.929

Lindemeyer, R. G., Gibson, C. W., and Wright, T. J. (2010). Amelogenesis imperfecta due to a mutation of the enamelin gene: Clinical case with genotype-phenotype correlations. *Pediatr. Dent.* 32 (1), 56–60.

Lu, T., Li, M., Xu, X., Xiong, J., Huang, C., Zhang, X., et al. (2018). Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders. *Int. J. Oral Sci.* 10, 26. doi:10.1038/s41368-018-0027-9

Ludwig, M.-G., Vanek, M., Guerini, D., Gasser, J. A., Jones, C. E., Junker, U., et al. (2003). Proton-sensing G-protein-coupled receptors. *Nature* 425, 93–98. doi:10.1038/nature01905

Maas, S. M., Jong, T. P. V. M. de, Buss, P., and Hennekam, R. C. M. (1996). EEC syndrome and genitourinary anomalies: An update. *Am. J. Med. Genet.* 63, 472–478. doi:10.1002/(SICI)1096-8628(19960614)63:3<472::AID-AJMG11>3.0

Márdh, C. K., Bäckman, B., Holmgren, G., Hu, J. C., Simmer, J. P., and Forsman-Semb, K. (2002). A nonsense mutation in the enamelin gene causes local hypoplastic autosomal dominant amelogenesis imperfecta (AIH2). *Hum. Mol. Genet.* 11(9), 1069–1074. doi:10.1093/hmg/11.9.1069

Martelli-Júnior, H., dos Santos Neto, P. E., de Aquino, S. N., de Oliveira Santos, C. C., Borges, S. P., Oliveira, E. A., et al. (2011). Amelogenesis imperfecta and nephrocalcinosis syndrome: A case report and review of the literature. *Nephron Physiol.* 118 (3), 62–65. doi:10.1159/000322828

Martino, F., D'Eufemia, P., Pergola, M. S., Finocchiaro, R., Celli, M., Giampà, G., et al. (1992). Child with manifestations of dermotrichic syndrome and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome. *Am. J. Med. Genet.* 44, 233–236. doi:10.1002/ajmg.132040222

Masunaga, T. (2006). Epidermal basement membrane: Its molecular organization and blistering disorders. *Connect. Tissue Res.* 47, 55–66. doi:10.1080/03008200600584517

Mátyás, G., Arnold, E., Carrel, T., Baumgartner, D., Boileau, C., Berger, W., et al. (2006). Identification and *in silico* analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders. *Hum. Mutat.* 27, 760–769. doi:10.1002/humu.20353

McCarl, C.-A., Picard, C., Khalil, S., Kawasaki, T., Röther, J., Papolos, A., et al. (2009). ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia. *J. Allergy Clin. Immunol.* 124, 1311–1318. doi:10.1016/j.jaci.2009.10.007

McGrath, J. A., Li, K., Dunnill, M. G. S., McMillan, J. R., Christiano, A. M., Eady, R. A., et al. (1996). Compound heterozygosity for a dominant Glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition. *Am. J. Pathol.* 148 (6), 1787–1796.

McNally, B. A., Somasundaram, A., Yamashita, M., and Prakriya, M. (2012). Gated regulation of CRAC channel ion selectivity by STIM1. *Nature* 482, 241–245. doi:10.1038/nature10752

Mechaussier, S., Perrault, I., Dollfus, H., Bloch-Zupan, A., Loundon, N., Jonard, L., et al. (2020). Heimler syndrome. *Adv. Exp. Med. Biol.* 1299, 81–87. doi:10.1007/978-3-030-62024-8_7

Mendoza, G., Pemberton, T. J., Lee, K., Scarel-Caminaga, R., Mehrian-Shai, R., Gonzalez-Quevedo, C., et al. (2007). A new locus for autosomal dominant amelogenesis imperfecta on chromosome 8q24.3. *Hum. Genet.* 120, 653–662. doi:10.1007/s00439-006-0246-6

Molla, M., Descroix, V., Aïoub, M., Simon, S., Castañeda, B., Hotton, D., et al. (2010). Enamel protein regulation and dental and periodontal physiopathology in Msx2 mutant mice. *Am. J. Pathol.* 177, 2516–2526. doi:10.2353/ajpath.2010.091224

Montaño, A. M., Tomatsu, S., Brusius, A., Smith, M., and Orii, T. (2008). Growth charts for patients affected with Morquio A disease. *Am. J. Med. Genet. Part A* 146A, 1286–1295. doi:10.1002/ajmg.a.32281

Mory, A., Dagan, E., Illi, B., Duquesnoy, P., Mordechai, S., Shahor, I., et al. (2012). A nonsense mutation in the human homolog of Drosophila rogdi causes koehschutter–tonz syndrome. *Am. J. Hum. Genet.* 90, 708–714. doi:10.1016/j.ajhg.2012.03.005

Müller, D., Kausalya, P. J., Meij, I. C., and Hunziker, W. (2006). Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: Blocking endocytosis restores surface expression of a novel claudin-16 mutant that lacks the entire C-terminal cytosolic tail. *Hum. Mol. Genet.* 15, 1049–1058. doi:10.1093/hmg/ddl020

Muto, T., Miyoshi, K., Horiguchi, T., and Noma, T. (2012). Dissection of morphological and metabolic differentiation of ameloblasts via ectopic SP6 expression. *J. Med. Investig.* 59, 59–68. doi:10.2152/jmi.59.59

Nagamine, K., Peterson, P., Scott, H. S., Kudoh, J., Minoshima, S., Heino, M., et al. (1997). Positional cloning of the APECED gene. *Nat. Genet.* 17, 393–398. doi:10.1038/ng1297-393

Nakamura, T., de Vega, S., Fukumoto, S., Jimenez, L., Unda, F., and Yamada, Y. (2008). Transcription factor epiprofin is essential for tooth morphogenesis by regulating epithelial cell fate and tooth number. *J. Biol. Chem.* 283, 4825–4833. doi:10.1074/jbc.M708388200

Nakamura, T., Unda, F., de-Vega, S., Vilaxa, A., Fukumoto, S., Yamada, K. M., et al. (2004). The Krüppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation. *J. Biol. Chem.* 279, 626–634. doi:10.1074/jbc.M307502200

Nalbant, D., Youn, H., Nalbant, S. I., Sharma, S., Cobos, E., Beale, E. G., et al. (2005). FAM20: An evolutionarily conserved family of secreted proteins expressed in hematopoietic cells. *BMC Genomics* 6, 11. doi:10.1186/1471-2164-6-11

Neuhaus, C., Eisenberger, T., Decker, C., Nagl, S., Blank, C., Pfister, M., et al. (2017). Next-generation sequencing reveals the mutational landscape of clinically diagnosed usher syndrome: Copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in heimler syndrome. *Mol. Genet. Genomic Med.* 5, 531–552. doi:10.1002/mgg3.312

Nikolopoulos, G., Smith, C. E. L., Brookes, S. J., El-Asrag, M. E., Brown, C. J., Patel, A., et al. (2020). New missense variants in RELT causing hypomineralised amelogenesis imperfecta. *Clin. Genet.* 97, 688–695. doi:10.1111/cge.13721

Nikolopoulos, G., Smith, C. E. L., Poulter, J. A., Murillo, G., Silva, S., Lamb, T., et al. (2021). Spectrum of pathogenic variants and founder effects in amelogenesis imperfecta associated with MMP20. *Hum. Mutat.* 42, 567–576. doi:10.1002/humu.24187

Noor, A., Windpassinger, C., Vitcu, I., Orlic, M., Rafiq, M. A., Khalid, M., et al. (2009). Oligodendonia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3. *Am. J. Hum. Genet.* 84, 519–523. doi:10.1016/j.ajhg.2009.03.007

Nurbaeva, M. K., Eckstein, M., Concepcion, A. R., Smith, C. E., Srikanth, S., Paine, M. L., et al. (2015). Dental enamel cells express functional SOCE channels. *Sci. Rep.* 5, 15803. doi:10.1038/srep15803

Ogawa, T., Tomatsu, S., Fukuda, S., Yamagishi, A., Rezvi, G. M., Sukegawa, K., et al. (1995). Mucopolysaccharidosis IVA: Screening and identification of mutations of the N-acetylgalactosamine-6-sulfate sulfatase gene. *Hum. Mol. Genet.* 4, 341–349. doi:10.1093/hmg/4.3.341

O'Sullivan, J., Bitu, C. C., Daly, S. B., Urquhart, J. E., Barron, M. J., Bhaskar, S. S., et al. (2011). Whole-Exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome. *Am. J. Hum. Genet.* 88, 616–620. doi:10.1016/j.ajhg.2011.04.005

Ozdemir, D., Hart, P. S., Firatli, E., Aren, G., Ryu, O. H., and Hart, T. C. (2005a). Phenotype of ENAM mutations is dosage-dependent. *J. Dent. Res.* 84, 1036–1041. doi:10.1177/154405910508401113

Ozdemir, D., Hart, P. S., Ryu, O. H., Choi, S. J., Ozdemir-Karatas, M., Firatli, E., et al. (2005b). MMP20 active-site mutation in hypomaturation amelogenesis imperfecta. *J. Dent. Res.* 84, 1031–1035. doi:10.1177/154405910508401112

Papagerakis, P., Lin, H.-K., Lee, K. Y., Hu, Y., Simmer, J. P., Bartlett, J. D., et al. (2008). Premature stop codon in MMP20 causing amelogenesis imperfecta. *J. Dent. Res.* 87, 56–59. doi:10.1177/154405910808700109

Parker, N. J., Begley, C. G., Smith, P. J., and Fox, R. M. (1996). Molecular cloning of a novel human gene (D11S4896E) at chromosomal region 11p15.5. *Genomics* 37, 253–256. doi:10.1006/geno.1996.0553

Parry, D. A., Brookes, S. J., Logan, C. V., Poulter, J. A., El-Sayed, W., Al-Bahlani, S., et al. (2012). Mutations in C4orf26, encoding a peptide with *in vitro* hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta. *Am. J. Hum. Genet.* 91, 565–571. doi:10.1016/j.ajhg.2012.07.020

Parry, D. A., Holmes, T. D., Gamper, N., El-Sayed, W., Hettiarachchi, N. T., Ahmed, M., et al. (2016a). A homozygous STIM1 mutation impairs store-operated calcium entry and natural killer cell effector function without clinical immunodeficiency. *J. Allergy Clin. Immunol.* 137, 955–957. doi:10.1016/j.jaci.2015.08.051

Parry, D. A., Mighell, A. J., El-Sayed, W., Shore, R. C., Jalili, I. K., Dollfus, H., et al. (2009). Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. *Am. J. Hum. Genet.* 84, 266–273. doi:10.1016/j.ajhg.2009.01.009

Parry, D. A., Poulter, J. A., Logan, C. V., Brookes, S. J., Jafri, H., Ferguson, C. H., et al. (2013). Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta. *Am. J. Hum. Genet.* 92, 307–312. doi:10.1016/j.ajhg.2013.01.003

Parry, D. A., Smith, C. E. L., El-Sayed, W., Poulter, J. A., Shore, R. C., Logan, C. V., et al. (2016b). Mutations in the pH-sensing G-protein-coupled receptor GPR68 cause amelogenesis imperfecta. *Am. J. Hum. Genet.* 99, 984–990. doi:10.1016/j.ajhg.2016.08.020

Pavlic, A., and Waltimo-Sirén, J. (2009). Clinical and microstructural aberrations of enamel of deciduous and permanent teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. *Arch. Oral Biol.* 54, 658–665. doi:10.1016/j.archoralbio.2009.03.009

Peracha, H., Sawamoto, K., Averill, L., Kecskemethy, H., Theroux, M., Thacker, M., et al. (2018). Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA. *Mol. Genet. Metab.* 125, 18–37. doi:10.1016/j.ymgme.2018.05.004

Pereverzey, A., Komarova, S. V., Korcok, J., Armstrong, S., Tremblay, G. B., Dixon, S. J., et al. (2008). Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway. *Bone* 42, 150–161. doi:10.1016/j.bone.2007.08.044
Perniola, R. (2018). Twenty years of AIRE. *Front. Immunol.* 9, 98. doi:10.3389/fimmu. 2018.00098

Picard, C., McCarli, C.-A., Papolos, A., Khalil, S., Lüthy, K., Hivroz, C., et al. (2009). STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. *N. Engl. J. Med.* 360, 1971–1980. doi:10.1056/NEJMoa0900082

Plaisancié, J., Collet, C., Pelletier, V., Perdomo, Y., Studer, F., Fradin, M., et al. (2015). MSX2 gene duplication in a patient with eye development defects. *Ophthalmic Genet.* 36, 353–358. doi:10.3109/13816810.2014.886270

Pollak, C., Floy, M., and Say, B. (2003). Sensorineural hearing loss and enamel hypoplasia with subtle nail findings: Another family with heimler's syndrome. *Clin. Dysmorphol.* 12, 55–58. doi:10.1097/00019605-200301000-00010

Polok, B., Escher, P., Ambresin, A., Chouery, E., Bolay, S., Meunier, I., et al. (2009). Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta. *Am. J. Hum. Genet.* 84, 259–265. doi:10.1016/j.ajhg.2009.01.006

Portsteffen, H., Beyer, A., Becker, E., Epplen, C., Pawlak, A., Kunau, W.-H., et al. (1997). Human PEX1 is mutated in complementation group 1 of the peroxisome biogenesis disorders. *Nat. Genet.* 17, 449–452. doi:10.1038/ng1297-449

Poulter, J. A., Brookes, S. J., Shore, R. C., Smith, C. E. L., Abi Farraj, L., Kirkham, J., et al. (2014a). A missense mutation in ITGB6 causes pitted hypomineralized amelogenesis imperfecta. *Hum. Mol. Genet.* 23, 2189–2197. doi:10.1093/hmg/ddt616

Poulter, J. A., Murillo, G., Brookes, S. J., Smith, C. E. L., Parry, D. A., Silva, S., et al. (2014b). Deletion of ameloblaston exon 6 is associated with amelogenesis imperfecta. *Hum. Mol. Genet.* 23, 5317–5324. doi:10.1093/hmg/duu247

Prasad, M. K., Geoffroy, V., Vicaire, S., Jost, B., Dumas, M., Le Gras, S., et al. (2016a). A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement. *J. Med. Genet.* 53, 98–110. doi:10.1136/ jmedgenet-2015-103302

Prasad, M. K., Laouina, S., El Alloussi, M., Dollfus, H., and Bloch-Zupan, A. (2016b). Amelogenesis imperfecta: 1 family, 2 phenotypes, and 2 mutated genes. *J. Dent. Res.* 95, 1457–1463. doi:10.1177/0022034516663200

Price, J. A., Bowden, D. W., Tim Wright, J., Pettenati, M. J., and Hart, T. C. (1998). Identification of a mutation in DLX3 associated with tricho-dento-osoiese (TDO) syndrome. *Hum. Mol. Genet.* 7, 563–569. doi:10.1093/hmg/7.3.563

Raine, J., Winter, R. M., Davey, A., and Tucker, S. M. (1989). Unknown syndrome: Microcephaly, hypoplastic nose, exophthalmos, gum hyperplasia, cleft palate, low set ears, and osteosclerosis. *J. Med. Genet.* 26, 786–788. doi:10.1136/jmg.26.12.786

Rao, S., and Witkop, C. J. (1971). Inherited defects in tooth structure. *Birth Defects Orig. Artic. Ser.* 7, 153–184.

Rapp, R. S., and Hodgkin, W. E. (1968). Anhidrotic ectodermal dysplasia: Autosomal dominant inheritance with palate and lip anomalies. *J. Med. Genet.* 5, 269–272. doi:10. 1136/jmg.5.4.269

Ratbi, I., Falkenberg, K. D., Sommen, M., Al-Sheqah, N., Guoaoua, S., Vandeweyer, G., et al. (2015). Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. *Am. J. Hum. Genet.* 97, 535–545. doi:10.1016/j.ajhg.2015.08.011

Rathi, N., Mattoo, K., and Bhatnagar, S. (2014). Extending the use of a diagnostic occlusal splint to overcome existing lacunae of vertical dimension transfer in full mouth rehabilitation cases. *Am. J. Med. Case Rep.* 2, 291–297. doi:10.12691/ajmcr-2-12-9

Reese, M. G., Eeckman, F. H., Kulp, D., and Haussler, D. (1997). Improved splice site detection in Genie. *J. Comput. Biol.* 4, 311–323. doi:10.1089/cmb.1997.4.311

Reuber, B. E., Germain-Lee, E., Collins, C. S., Morrell, J. C., Ameritunga, R., Moser, H. W., et al. (1997). Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. *Nat. Genet.* 17, 445–448. doi:10.1038/ng1297-445

Rey, T., Tarabeux, J., Gerard, B., Delbarre, M., Le Béchec, A., Stoetzel, C., et al. (2019). Protocol GenoDENT: Implementation of a new NGS panel for molecular diagnosis of genetic disorders with orodental involvement. *Methods Mol. Biol.* 1922, 407–452. doi:10.1007/978-1-4939-9012-2_36

Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., et al. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular pathology. *Genet. Med.* 17, 405–424. doi:10.1038/gim.2015.30

Rinne, T., Hamel, B., van Bokhoven, H., and Brunner, H. G. (2006). Pattern of p63 mutations and their phenotypes-update. *Am. J. Med. Genet.* A 140, 1396–1406. doi:10.1002/ajmg.a.31271

Robinson, C. (2014). Enamel maturation: A brief background with implications for some enamel dysplasias. *Front. Physiol.* 5, 388. doi:10.3389/fphys.2014.00388

Rolling, I., Clausen, N., Nyyad, B., and Sindet-Pedersen, S. (1999). Dental findings in three siblings with Morquio's syndrome. *Int. J. Paediatr. Dent.* 9, 219–224. doi:10.1046/ j.1365-263x.1999.00127.x

Ruspita, I., Das, P., Xia, Y., Kelangi, S., Miyoshi, K., Noma, T., et al. (2020). An msx2-sp6-follistatin pathway operates during late stages of tooth development to control amelogenesis. *Front. Physiol.* 11, 582610. doi:10.3389/fphys.2020.582610

Sabbioni, S., Veronese, A., Trubia, M., Taramelli, R., Barbanti-Brodano, G., Croce, C. M., et al. (1999). Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD. *Cytogenet Cell Genet.* 86, 214–218. doi:10.1159/000015341

Sawamoto, K., Álvarez González, J. V., Piechnik, M., Otero, F. J., Couce, M. L., Suzuki, Y., et al. (2020). Mucopolysaccharidosis IVA: Diagnosis, treatment, and management. *Int. J. Mol. Sci.* 21. 1517. doi:10.3390/ijms21041517

Scherer, S. W., Heng, H. H. Q., Robinson, G. W., Mahon, K. A., Evans, J. P., and Tsui, L.-C. (1995). Assignment of the human homolog of mouse Dlx3 to Chromosome 17q21.3-q22 by analysis of somatic cell hybrids and fluorescence *in situ* hybridization. *Mamm. Genome* 6, 310–311. doi:10.1007/BF00352432

Schossig, A., Bloch-Zupan, A., Lussi, A., Wolf, N. I., Raskin, S., Cohen, M., et al. (2017). SLC13A5 is the second gene associated with Kohlschütter-Tönz syndrome. *J. Med. Genet.* 54, 54–62. doi:10.1136/jmedgenet-2016-103988

Schossig, A., Wolf, N. I., Fischer, C., Fischer, M., Stocker, G., Pabinger, S., et al. (2012). Mutations in ROGDI cause kohlschütter-tönz syndrome. *Am. J. Hum. Genet.* 90, 701–707. doi:10.1016/j.ajhg.2012.02.012

Schulze, C. (1970). "Developmental abnormalities of the teeth and jaws," in *Thoma's oral pathology*. Editors R. J. Gorlin and H. M. Goldman (St Louis: C. V. Mosby), 112–122.

Sewerin, S., Piontek, J., Schönauer, R., Grunewald, S., Rauch, A., Neuber, S., et al. (2022). Defective claudin-10 causes a novel variation of HELIX syndrome through compromised tight junction strand assembly. *Genes. Dis.* 9, 1301–1314. doi:10.1016/j. gendis.2021.06.006

Seymen, F., Kim, Y. J., Lee, Y. J., Kang, J., Kim, T.-H., Choi, H., et al. (2016). Recessive mutations in ACPT, encoding testicular acid phosphatase, cause hypoplastic amelogenesis imperfecta. *Am. J. Hum. Genet.* 99, 1199–1205. doi:10.1016/j.ajhg. 2016.09.018

Seymen, F., Lee, K.-E., Koruyucu, M., Gencay, K., Bayram, M., Tuna, E. B., et al. (2014a). ENAM mutations with incomplete penetrance. *J. Dent. Res.* 93, 988–992. doi:10.1177/0022034514548222

Seymen, F., Lee, K.-E., Tran Le, C. G., Yildirim, M., Gencay, K., Lee, Z. H., et al. (2014b). Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta. *J. Dent. Res.* 93, 366–370. doi:10.1177/0022034514523786

Seymen, F., Lee, K.-E., Tran Le, C. G., Yildirim, M., Gencay, K., Lee, Z. H., et al. (2014b). Exonal deletion of SLC24A4 causes hypomaturation amelogenesis imperfecta. *J. Dent. Res.* 93, 366–370. doi:10.1177/0022034514523786

Seymen, F., Park, J.-C., Lee, K.-E., Lee, H.-K., Lee, D.-S., Koruyucu, M., et al. (2015b). Novel MMP20 and KLK4 mutations in amelogenesis imperfecta. *J. Dent. Res.* 94, 1063–1069. doi:10.1177/0022034515590569

Seymen, F., Zhang, H., Kasimoglu, Y., Koruyucu, M., Simmer, J. P., Hu, J. C.-C., et al. (2021). Novel mutations in GPR68 and SLC24A4 cause hypomaturation amelogenesis imperfecta. *J. Pers. Med.* 12, 13. doi:10.3390/jpm12010013

Shaheen, R., Ansari, S., Alshammari, M. J., Alkhalidi, H., Alrukban, H., Eyaid, W., et al. (2013). A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency. *J. Med. Genet.* 50, 431–436. doi:10.1136/jmedgenet- 2013-101527

Shapiro, M. B., and Senapathy, P. (1987). RNA splice junctions of different classes of eukaryotes: Sequence statistics and functional implications in gene expression. *Nucleic Acids Res.* 15, 7155–7174. doi:10.1093/nar/15.17.7155

Shore, R. C., Bäckman, B., Elcock, C., Brook, A. H., Brookes, S. J., and Kirkham, J. (2010). The structure and composition of deciduous enamel affected by local hypoplastic autosomal dominant amelogenesis imperfecta resulting from an ENAM mutation. *Cells Tissues Organs* 191, 301–306. doi:10.1159/000258703

Simmer, J. P., Hu, J. C.-C., Hu, Y., Zhang, S., Liang, T., Wang, S.-K., et al. (2021). A genetic model for the secretory stage of dental enamel formation. *J. Struct. Biol.* 213, 107805. doi:10.1016/j.jsb.2021.107805

Simmer, J. P., Hu, Y., Lertlam, R., Yamakoshi, Y., and Hu, J. C.-C. (2009). Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice. *J. Biol. Chem.* 284, 19110–19121. doi:10.1074/jbc.M109.013623

Simon, D. B., Lu, Y., Choate, K. A., Velazquez, H., Al-Sabban, E., Praga, M., et al. (1999). Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. *Science* 285, 103–106. doi:10.1126/science.285.5424.103

Simpson, M. A., Hsu, R., Keir, L. S., Hao, J., Sivapalan, G., Ernst, L. M., et al. (2007). Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development. *Am. J. Hum. Genet.* 81, 906–912. doi:10.1086/522240

Simpson, M. A., Scheuerle, A., Hurst, J., Patton, M. A., Stewart, H., and Crosby, A. H. (2009). Mutations in FAM20C also identified in non-lethal osteosclerotic bone dysplasia. *Clin. Genet.* 75, 271–276. doi:10.1111/j.1399-0004.2008.01118.x

Slegtenhorst, M. van, Hoogt, R. de, Hermans, C., Nellist, M., Janssen, B., Verhoef, S., et al. (1997). Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. *Science* 277, 805–808. doi:10.1126/science.277.5327.805
Smith, C. E. L., Kirkham, J., Day, P. F., Soldani, F., McDerra, E. J., Poulter, J. A., et al. (2017a). A fourth KLK4 mutation is associated with enamel hypomineralisation and structural abnormalities. *Front. Physiol.* 8, 333. doi:10.3389/fphys.2017.00333

Smith, C. E. L., Murillo, G., Brookes, S. J., Poulter, J. A., Silva, S., Kirkham, J., et al. (2016). Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta. *Hum. Mol. Genet.* 25, 3578-3587. doi:10.1093/hmg/ddw203

Smith, C. E. L., Poulter, J. A., Brookes, S. J., Murillo, G., Silva, S., Brown, C. J., et al. (2019). Phenotype and variant spectrum in the LAMB3 form of amelogenesis imperfecta. *J. Dent. Res.* 98, 698-704. doi:10.1177/0022034519835205

Smith, C. E. L., Whitehouse, L. L. E., Poulter, J. A., Wilkinson Hewitt, L., Nadat, F., Jackson, B. R., et al. (2020). A missense variant in specificity protein 6 (SP6) is associated with amelogenesis imperfecta. *Hum. Mol. Genet.* 29, 1417-1425. doi:10.1093/hmg/ddaa041

Smith, C. E., Whitehouse, L. L., Poulter, J. A., Brookes, S. J., Day, P. F., Soldani, F., et al. (2017b). Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta. *Eur. J. Hum. Genet.* 25, 1015-1019. doi:10.1038/ejhg.2017.79

Spedicati, B., Cocca, M., Palmisano, R., Faletra, F., Barbieri, C., Francescatto, M., et al. (2021). Natural human knockouts and mendelian disorders: Deep phenotyping in Italian isolates. *Eur. J. Hum. Genet.* 29, 1272-1281. doi:10.1038/s41431-021-00850-9

Sripathomsawat, W., Tanpaiboon, P., Heering, J., Dötsch, V., Hennekam, R. C. M., and Kantaputra, P. (2011). Phenotypic analysis of Arg227 mutations of TP63 with emphasis on dental phenotype and micturition difficulties in EEC syndrome. *Am J M Genet A* 155, 228-232. doi:10.1002/ajmg.a.33768

Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., et al. (2010). TAP63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. *Nature* 467, 986-990. doi:10.1038/nature09459

Suh, J., Choi, H. S., Kwon, A., Chae, H. W., Lee, J.-S., and Kim, H.-S. (2019). A novel compound heterozygous mutation of the AIRE gene in a patient with autoimmune polyendocrine syndrome type 1. *Ann. Pediatr. Endocrinol. Metab.* 24, 248-252. doi:10.6065/apem.2019.24.4.248

Sun, S., Yu, M., Fan, Z., Yeh, I.-T., Feng, H., Liu, H., et al. (2019). DLX3 regulates osteogenic differentiation of bone marrow mesenchymal stem cells via Wnt/β-catenin pathway mediated histone methylation of DKK4. *Biochem. Biophys. Res. Commun.* 516, 171-176. doi:10.1016/j.bbrc.2019.06.029

Sutton, V. R., and van Bokhoven, H. (2010). "TP63-Related disorders," in *GeneReviews® [Internet]*. Editors M. P. Adam, D. B. Everman, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, L. J. H. Bean, et al. (Seattle (WA): University of Washington, Seattle), 1993-2022.

Tabata, M. J., Matsumura, T., Liu, J. G., Wakisaka, S., and Kurisu, K. (1996). Expression of cytokeratin 14 in ameloblast-lineage cells of the developing tooth of rat, both *in vivo* and *in vitro*. *Arch. Oral Biol.* 41, 1019-1027. doi:10.1016/s0003-9969(96)00087-8

Tanaka, A., Weinel, S., Nagy, N., O'Driscoll, M., Lai-Cheong, J. E., Kulp-Shorten, C. L., et al. (2012). Germline mutation in ATR in autosomal-dominant oropharyngeal cancer syndrome. *Am. J. Hum. Genet.* 90, 511-517. doi:10.1016/j.ajhg.2012.01.007

Tanimoto, K., Le, T., Zhu, L., Witkowska, H. E., Robinson, S., Hall, S., et al. (2008). Reduced amelogenin-MMP20 interactions in amelogenesis imperfecta. *J. Dent. Res.* 87, 451-455. doi:10.1177/154409510808700516

The 1000 Geno; mes Project ConsortiumGibbs, R. A., Boerwinkle, E., Doddapaneni, H., Han, Y., Korchina, V., et al. (2015). A global reference for human genetic variation. *Nature* 526, 68-74. doi:10.1038/nature15393

Tomura, H., Wang, J.-Q., Liu, J.-P., Komachi, M., Damirin, A., Mogi, C., et al. (2008). Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line. *J. Bone Min. Res.* 23, 1129-1139. doi:10.1359/jbmr.080236

Torres, L. H. S., de-Azevedo-Vaz, S. L., Barroso, D. R. C., Silva, D. N., Velloso, T. R. G., and de Barros, L. A. P. (2018). Enamel-renal-syndrome: Case report. *Spec. Care Dent.* 38 (3), 172-175. doi:10.1111/scd.12288

Toysawa, S., Fujiwara, T., Ooshima, T., Shintani, S., Sato, A., Ogawa, Y., et al. (2000). Cloning and characterization of the human ameloblastin gene. *Gene* 256, 1-11. doi:10.1016/S0378-1119(00)00379-6

Tucci, A., Kara, E., Schossig, A., Wolf, N. I., Plagnol, V., Fawcett, K., et al. (2013). Kohlschütter-Tönz syndrome: Mutations in ROGDI and evidence of genetic heterogeneity. *Hum. Mutat.* 34 (2), 296-300. doi:10.1002/humu.22241

Utami, T. W., Miyoshi, K., Hagita, H., Yanuaryska, R. D., Horiguchi, T., and Noma, T. (2011). Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization. *J. Biomed. Biotechnol.* 2011, 320987. doi:10.1155/2011/320987

Vahidnezhad, H., Youssefian, L., Zeinali, S., Saeidian, A. H., Sotoudeh, S., Mozafari, N., et al. (2017). Dystrophic epidermolysis bullosa: COL7A1 mutation landscape in a multi-ethnic cohort of 152 extended families with high degree of customary consanguineous marriages. *J. Investig. Dermatol* 137, 660-669. doi:10.1016/j.jid.2016.10.023

van Bakel, I., Sepp, T., Ward, S., Yates, J. R. W., and Green, A. J. (1997). Mutations in the TSC2 gene: Analysis of the complete coding sequence using the protein truncation test (PTT). *Hum. Mol. Genet.* 6, 1409-1414. doi:10.1093/hmg/6.9.1409

Vieira, G. H., Rodriguez, J. D., Carmona-Mora, P., Cao, L., Gamba, B. F., Carvalho, D. R., et al. (2012). Detection of classical 17p11.2 deletions, an atypical deletion and

RAII alterations in patients with features suggestive of Smith-Magenis syndrome. *Eur. J. Hum. Genet.* 20, 148-154. doi:10.1038/ejhg.2011.167

Vig, M., Peinelt, C., Beck, A., Koomoa, D. L., Rabah, D., Koblan-Huberson, M., et al. (2006). CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. *Science* 312, 1220-1223. doi:10.1126/science.1127883

Wang, S.-K., Choi, M., Richardson, A. S., Reid, B. M., Lin, B. P., Wang, S. J., et al. (2014b). ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta. *Hum. Mol. Genet.* 23, 2157-2163. doi:10.1093/hmg/ddt611

Wang, S.-K., Hu, Y., Simmer, J. P., Seymen, F., Estrella, N. M. R. P., Pal, S., et al. (2013). Novel KLK4 and MMP20 mutations discovered by whole-exome sequencing. *J. Dent. Res.* 92, 266-271. doi:10.1177/0022034513475626

Wang, S.-K., Zhang, H., Chavez, M. B., Hu, Y., Seymen, F., Koruyucu, M., et al. (2020). Dental malformations associated with biallelic MMP20 mutations. *Mol. Genet. Genomic Med.* 8, e1307. doi:10.1002/mgg3.1307

Wang, S., Choi, M., Richardson, A. S., Reid, B. M., Seymen, F., Yildirim, M., et al. (2014a). STIM1 and SLC24A4 are critical for enamel maturation. *J. Dent. Res.* 93, 94S-100S-100S. doi:10.1177/0022034514527971

Wang, X., Zhao, Y., Yang, Y., and Qin, M. (2015). Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta. *PLoS One* 10, e0116514. doi:10.1371/journal.pone.0116514

Wazen, R. M., Viegas-Costa, L. C., Fouillen, A., Moffatt, P., Adair-Kirk, T. L., Senior, R. M., et al. (2016). Laminin γ2 knockout mice rescued with the human protein exhibit enamel maturation defects. *Matrix Biol.* 52 (54), 207-218. doi:10.1016/j.matbio.2016.03.002

Weinmann, J. P., Svoboda, J. F., and Woods, R. W. (1945). Hereditary disturbances of enamel formation and calcification**. From the research department, loyola university, school of Dentistry, Chicago College of dental surgery, and the department of health and welfare, bureau of health, division of dental health, augusta, Maine. *J. Am. Dent. Assoc.* 32, 397-418. doi:10.14219/jada.archive.1945.0063

Whitehouse, L. L. E., Smith, C. E. L., Poulter, J. A., Brown, C. J., Patel, A., Lamb, T., et al. (2019). Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome. *Oral Dis.* 25, 182-191. doi:10.1111/odi.12955

Wimalarathna, A., Abeyasinghe, U., Jayasooriya, P., and Herath, C. (2020). Amelogenesis imperfecta: A literature review based guide to diagnosis and management. *J. M. Dent.* 10, 94-101. doi:10.4687/jmd.v10i3.532

Witkop, C. J. (1988). Amelogenesis imperfecta, dentinogenesis imperfecta and dentin dysplasia revisited: Problems in classification. *J. Oral Pathol.* 17, 547-553. doi:10.1111/j.1600-0714.1988.tb01332.x

Witkop, C. J. (1957). Hereditary defects in enamel and dentin. *Acta Genet. Stat. Med.* 7, 236-239. doi:10.1159/000150974

Witkop, C. J. (1971). Manifestations of genetic diseases in the human pulp. *Oral Surg. Oral Med. Oral Pathol.* 32, 278-316. doi:10.1016/0030-4220(71)90232-5

Witkop, C. J., and Sauk, J. J. (1976). "Heritable defects of enamel," in *Oral facial genetics*. Editors R. Stewart and G. Prescott (St. Louis: C.V. Mosby Company), 151-226.

Wright, J. T., Carrion, I. A., and Morris, C. (2015). The molecular basis of hereditary enamel defects in humans. *J. Dent. Res.* 94, 52-61. doi:10.1177/0022034514556708

Wright, J. T. (2023). Enamel phenotypes: Genetic and environmental determinants. *Genes* 14, 545. doi:10.3390/genes14030545

Wright, J. T., Puranik, C. P., and Farrington, F. (1961). Oral phenotype and variation in focal dermal hypoplasia. *Am. J. Med. Genet. C Semin. Med. Genet.* 172C, 52-58. doi:10.1002/ajmg.c.31478

Yamada, N., Fukuda, S., Tomatsu, S., Muller, V., Hopwood, J. J., Nelson, J., et al. (1998). Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern Ireland: Nine novel mutations including T312S, a common allele that confers a mild phenotype. *Hum. Mutat.* 11 (3), 202-208. doi:10.1002/(SICI)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J

Yamaguti, P. M., Neves, F. de A. R., Hotton, D., Bardet, C., Dure-Molla, M. de L., Castro, L. C., et al. (2017). Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations. *J. Med. Genet.* 54, 26-37. doi:10.1136/jmedgenet-2016-103956

Yamazaki, D., Funato, Y., Miura, J., Sato, S., Toyosawa, S., Furutani, K., et al. (2013). Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: A mouse model. *PLoS Genet.* 9, e1003983. doi:10.1371/journal.pgen.1003983

Yang, A., Schweitzer, R., Sun, D., Kaghad, M., Walker, N., Bronson, R. T., et al. (1999). p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. *Nature* 398, 714-718. doi:10.1038/19539

Yang, M., Mailhot, G., Birnbaum, M. J., MacKay, C. A., Mason-Savas, A., and Odgren, P. R. (2006). Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis. *J. Biol. Chem.* 281, 23598-23605. doi:10.1074/jbc.M602191200

Yenamandra, V. K., Vellarikkal, S. K., Chowdhury, M. R., Jayarajan, R., Verma, A., Scaria, V., et al. (2018). Genotype-phenotype correlations of dystrophic epidermolysis
bullosa in India: Experience from a tertiary care centre. *Acta Derm. Venereol.* 98, 873-879. doi:10.2340/00015555-2929

Yeo, G., and Burge, C. B. (2004). Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. *J. Comput. Biol.* 11, 377–394. doi:10.1089/1066527041410418

Yuan, J. P., Zeng, W., Huang, G. N., Worley, P. F., and Muallem, S. (2007). STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels. *Nat. Cell. Biol.* 9, 636–645. doi:10.1038/ncb1590

Yuen, W. Y., Pasmooij, A. M. G., Stellingsma, C., and Jonkman, M. F. (2012). Enamel defects in carriers of a novel LAMA3 mutation underlying epidermolysis bullosa. *Acta Derm. Venereol.* 92, 695–696. doi:10.2340/00015555-1341

Zanetti, A., D'Avanzo, F., AlSayed, M., Brusius-Facchin, A. C., Chien, Y. H., Giugliani, R., et al. (2021). Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome):

A review and classification of GALNS gene variants and reporting of 68 novel variants. *Hum. Mutat.* 42 (11), 1384–1398. doi:10.1002/humu.24270

Zhang, H., Koruyucu, M., Seymen, F., Kasimoglu, Y., Kim, J.-W., Tinawi, S., et al. (2019). WDR72 mutations associated with amelogenesis imperfecta and acidosis. *J. Dent. Res.* 98, 541–548. doi:10.1177/0022034518824571

Zhang, Z., Suzuki, Y., Shimozawa, N., Fukuda, S., Imamura, A., Tsukamoto, T., et al. (1999). Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. *Hum. Mutat.* 13, 487–496. doi:10.1002/(SICI)1098-1004(1999)13:6<487::AID-HUMU9>3.0.CO;2-T

Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., and Sabatini, D. M. (2011). mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. *Science* 334, 678–683. doi:10.1126/science.1207056