Mi et al. BMC Pediatrics(2024) 24:528
https://doi.org/10.1186/s12887-024-04628-y

BMC Pediatrics

CASE REPORTOpen Access

Concurrent de novo MACF1 mutationand inherited 16p13.11 microduplication
in a preterm newborn with hypotonia,
joint hyperlaxity and multiple congenital
malformations: a case report
Lanlan Mi1, Ruen Yao2, Weiwei Guo1*, Jian Wang2*, Guoqing Zhang1 and Xiuxia Ye1
Abstract
Background The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell
movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb. The 16p13.11 microduplication
syndrome results from the duplication of 16p13.11 chromosome copies and is associated with various
neurodevelopmental and physiological abnormalities. Both MACF1 and 16p13.11 microduplication have significant
impacts on neural development, potentially leading to nerve damage or neurological diseases. This study presents
a unique case of a patient simultaneously experiencing a de novo MACF1 mutation and a hereditary 16p13.11
microduplication, which has not been reported previously.
Case presentation In this report, we describe a Chinese preterm newborn girl exhibiting the typical characteristics
of 16.13.11 microduplication syndrome. These features include developmental delay, respiratory issues, feedingproblems, muscle weakness, excessive joint movement, and multiple congenital abnormalities. Throughwhole-exome sequencing, we identified a disease-causing mutation in the MACF1 gene (c.15266T > C / p.
Met5089Thr). Additionally, after microarray analysis, we confirmed the presence of a 16p13.11 microduplication(chr16:14,916,289 − 16,315,688), which was inherited from the mother.
Conclusions The patient’s clinical presentation, marked by muscle weakness and multiple birth defects, may be
attributed to both the de novo MACF1 mutation and the 16p13.11 duplication, which could have further amplified
her severe symptoms. Genetic testing for individuals with complex clinical manifestations can offer valuable insights
for diagnosis and serve as a reference for genetic counseling for both patients and their families.
Keywords MACF1 mutation, 16p13.11 microduplication syndrome, Neonate, Congenital malformations*Correspondence:
Weiwei Guovivi_guo0578@163.com
Jian Wang
labwangjian@shsmu.edu.cn

1

Department of Neonatology, Shanghai Children’s Medical Center,
Shanghai Jiao Tong University School of Medicine, Shanghai, China
2
Department of Medical Genetics and Molecular Diagnostic Laboratory,
Shanghai Children’s Medical Center, Shanghai Jiao Tong University Schoolof Medicine, Shanghai, China© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) andthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in thisarticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not includedin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you willneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The
Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available
in this article, unless otherwise stated in a credit line to the data.

Mi et al. BMC Pediatrics(2024) 24:528

Background
MACF1 (Microtubule actin crosslinking factor 1) is alarge protein expressed in various tissues, with high levels found in the heart, skeletal muscles, intestine, colon,
and moderate levels in the brain and lungs [1]. Abnormal
expression of MACF1 can result in dysfunctional tissue
development and organ function across multiple organs.
MACF1 mutations are associated with neuromusculardisorders characterized by progressive spastic tetraplegia, dystonia, joint contractures, feeding difficulties, anddevelopmental delays [2]. Additionally, MACF1 plays arole in regulating osteoblast proliferation and differentiation [3], and its aberrant expression is linked to thedevelopment of several tumors due to increased cell proliferation [4].
The 16p13.11 microduplication is a recurring genetic
anomaly found not only in individuals with neurologicalimpairments but also in healthy individuals [5]. Clinicalmanifestations of this duplication include multiple congenital abnormalities and primarily neurodevelopmental disorders such as speech delays, learning disabilities,
attention-deficit/hyperactivity disorder, intellectual disabilities, developmental delays, and autistic spectrum
disorder (ASD) [6–9]. Furthermore, there is a notable
increased risk of cardiovascular diseases associated withthis duplication [6, 10].
In this study, we present the case of a female patient
who possesses a de novo MACF1 mutation alongside
a 16p13.11 duplication spanning 1300 kb. This patient
exhibits global developmental delay, respiratory distress,
feeding difficulties, and multiple dysmorphic features.
We also explore the combined effects of both genetic
abnormalities on the patient’s phenotype.
Case presentation
The patient is a female born to healthy, non-consanguineous parents with an unremarkable family history.
She was conceived through in vitro fertilization-embryotransplantation (IVF-ET) and was delivered via caesarean section at 33+5 weeks of gestation due to fetal growth
restriction, preeclampsia, and a prior hysteromyoma surgery. At birth, she weighed 1595 g (10th percentile) andhad an occipitofrontal circumference of 28 cm (5th percentile), indicating she was smaller than expected for her
gestational age.
The patient exhibited distinctive facial features, including a broad forehead, arched eyebrows, sunken eye sockets, small and slanted eye openings, corneal edema, a flat
nasal bridge, and upturned nostrils. Additionally, she had
a flat chest, an increased palmar crease on her right hand,and anteriorization of the anus close to the labia majora,
covered by a white film. Neurologically, she displayed
hypotonia, reduced light reflex in both eyes, absence ofPage 2 of 6

crying, decreased motor activity, and intracranial hemorrhage (Level IV).
Following birth, the patient experienced severe breathing difficulties, necessitating immediate intubation. She
was subsequently transferred to the NICU at ShanghaiChildren’s Medical Center, where she required invasive
mechanical ventilation for the first 18 days of life. Her
ECG indicated a slightly prolonged QT interval, andcardiac ultrasound revealed a patent ductus arteriosus(0.15 cm), an atrial septal defect (0.25 cm), and stable
hemodynamics.
The patient also developed significant feeding intolerance and gastric retention. Further assessments indicateddelayed gastric emptying and the possibility of digestive
tract malformation. Notably, she displayed excessive joint
mobility, with her leg angle exceeding 180 degrees.
a-CGH identified a duplication on the short arm ofchromosome 16 (chr16:14,916,289 − 16,315,688), which
was inherited from the mother (Fig. 1). Sanger sequencing confirmed the wild-type status of the MACF1 gene(c.15266T > C / p. Met5089Thr) mutation in the parents,
with the proband being heterozygous (Fig. 2). Machinelearning-based pathogenicity prediction of the MACF1
variants indicated their deleterious nature (0.98, 0.99)
according to Alpha Missense and DANN [11, 12]. Other
variants in the MACF1 gene, apart from the de novo
mutation, were excluded due to insufficient evidence of
pathogenicity (Supplementary Table 1).

Discussion and conclusions
MACF1, a member of the cytoskeleton cross-linking protein family, plays a crucial role in regulating the dynamics
of the cytoskeleton network. It exhibits high expression
levels in neuronal tissues and the foregut of embryonicday 8.5 (E8.5) embryos, as well as in the head fold andprimitive streak of E7.5 embryos [13]. The presence ofthe microtubule-binding growth-arrest-specific 2 domain
variant of MACF1 is a unique and likely contributor tobrain abnormalities, particularly severe dorsal-ventral
stenosis of the brainstem, primarily occurring in the pontine and midsagittal regions of the cerebellar eminence[14]. MACF1’s role in controlling neurite growth andbranching involves the regulation of actin and microtubule alignment and stability, mediating GSK3 signals. In
mice, the deletion of MACF1 has been associated withabnormalities in dendritic differentiation in cortical andhippocampal neurons [15]. In humans, MACF1 mutations may be inherited in an autosomal recessive manner,leading to spectraplakinopathy characterized by progressive spastic tetraplegia, dystonia, joint contractures, feeding difficulties, and developmental delays [2]. MACF1 isalso considered a potential novel recessive epilepsy gene[16]. It is associated with congenital myasthenia [17] andcongenital pulmonary airway malformations [18]. TheseMi et al. BMC Pediatrics(2024) 24:528

Page 3 of 6

Fig. 1 In the first chromosome, representing the proband (the patient), and the following two chromosomes, representing her father and mother, thered arrow points to the segment of chromosome 16 (chr16:14,916,289 − 16,315,688) microduplication

Fig. 2 The initial gene chain corresponds to the proband (the patient), and the subsequent two gene chains correspond to her father and mother, respectively. The red arrow indicates the presence of the MACF1 (c.15266T > C / p. Met5089Thr) mutation

factors collectively account for our patient’s intrauterine growth retardation, hypotonia, flat chest, abnormal
breathing, and feeding difficulties.
Cranial nerve defects resulting in dysphagia wereobserved in four children, while one child exhibited
asymmetric facial movements, three had strabismus, two
had cortical visual impairment, and one had left opticnerve hypoplasia [14]. Similar findings were reported
in another Japanese child [19]. May Simera et al. [20]demonstrated that the deletion of MACF1 in mice led
to impaired retinal delamination and lamination, as wellas halted photoreceptor maturation. Consistent withthese animal models, our patient experienced difficulty
feeding and displayed reduced light reflex in both eyes.

Furthermore, MACF1’s impact on osteoblast proliferation, differentiation, and bone formation may explain thebone deformities and excessive joint mobility observedin patients [21]. Due to its expression in multiple organs
and tissues, abnormal MACF1 expression is implicated in
the development of various tumors [22, 23].
In addition to the de novo MACF1 mutation, ourpatient also carried the maternal 16p13.11 duplication.
Copy number variations (CNVs) like this are typicallyinherited from seemingly healthy parents, often carriersof balanced translocations [24]. Homozygous forms ofthese rearrangements have been observed in individuals with various behavioral phenotypes, including intellectual disability, developmental delay, speech delay, andMi et al. BMC Pediatrics(2024) 24:528

emotional and behavioral disorders such as attentiondeficit/hyperactivity disorder and ASD [25, 26]. Additionally, neurodevelopmental abnormalities encompass
gross motor delay, epilepsy, and schizophrenia [26]. Somepatients with 16p13.11 microduplication have presented
with abnormal brain MRI findings, as well as cardiac andaortic/pulmonary malformations [6]. Notably, certain
individuals have exhibited prominent skeletal features
like craniosynostosis, polydactyly, and excessive joint
mobility [27].
Other medical conditions associated with 16p13.11
microduplication include a range of congenital abnormalities of varying severity, including distinctive facial
features [28] such as deep-set eyes [29], upslanting palpebral fissures, preauricular skin tags [26], and low-set
ears [27]. Microcephaly or macrocephaly, craniosynostosis, polydactyly, tall stature, pes planus, and vision issues
like strabismus, myopia, and amblyopia have also beenreported [24]. Some patients have shown intestinal malrotation and absent 12th ribs [30, 31].
The neonatal neurodevelopmental phenotype associated with this microduplication often includes hypotonia, feeding difficulties, and respiratory problems [6, 24].
Unfortunately, our newborn patient only survived for 18
days after birth and displayed multiple congenital malformations, hypotonia, excessive joint mobility, feeding
difficulties, respiratory problems, and cardiac malformations, consistent with previous reports. However, her
phenotype was more severe due to the combined effectsof the MACF1 mutation and the 16p13.11 microduplication. In continuous genetic syndromes, while naturally conceived children may have genetic abnormalities,
assisted reproductive techniques (ART) can increase thelikelihood of epigenomic defects [32, 33]. It’s important
to consider the potential impact of ART on our patient’s
phenotype. Epigenetics is influenced by various factors,
and even overlapping or very similar genetic changes canlead to phenotypic variations, resulting in varying disease
severity [34]. Therefore, studying more cases can contribute to a better understanding of the genotype-phenotype
correlation.
The varied clinical manifestations seen in 16p13.11
microduplication syndrome may be attributed to different genes within this region, which contains 13 distinct
OMIM genes [28]. These genes include ABCC1, ABCC6,
CEP20, MARF1, MPV17L, MYH11, NDE1, NOMO1,NOMO3, NPIPA1, NTAN1, PDXDC1, and RRN3. Notably, NDE1 plays a crucial role in microtubule organization, mitosis, and neuronal migration [35]. Changes in
its dosage can result in secondary genomic damage tocortical neurons [36], making it a prime candidate genefor the neurological and behavioral phenotypes observedin affected patients [37, 38]. Additionally, miR-484 also
plays a vital role in the neurocognitive phenotype [25],Page 4 of 6

and MYH11 has been identified in familial cases of aortic aneurysms with an elevated risk of dissection [10, 39].
However, the roles and mechanisms of the other genes
in the 16p13.11 duplication syndrome remain unclear,necessitating further research.
Many of the clinical features observed in our patientalign with those found in previous cases affected byeither MACF1 mutation or 16p13.11 microduplication
syndrome. Moreover, our patient’s phenotype was more
severe, likely due to the combined effects of both genetic
abnormalities. Interestingly, the presence of an increased
palmar crease is the first reported case in 16p13.11
microduplication syndrome. Expanding our understanding of the phenotypes associated with 16p13.11 duplication syndrome and their potential relationships withspecific genetic and genomic loci will contribute to further geno-phenotype research. Patients with concurrent
genomic variants on various scales are at risk of being
missed or misdiagnosed. An integrated genetic testing
and analysis approach, supported by a detailed description of the phenotype, can enhance diagnostic yield andlead to novel discoveries in clinical diagnostics [40, 41].
This report underscores the importance of thoroughly
analyzing the phenotypes of patients with complex
genotypes and provides additional insights and characterizations. We hope that this report can aid in genetic
counseling and further research in this field.
Abbreviations
MACF1	Microtubule action crossing factor 1
ASD	Autistic spectrum disorder
CNV	Copy number variation

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-04628-y.
Supplementary Material 1
Acknowledgements
We are grateful to the patient and her family for their collaboration.
Author contributions
MLL and GWW collected and analyzed the clinical data, and wrote
the manuscript. YRE and WJ performed all gene detection as well asbioinformatics analysis, and wrote the manuscript. MLL and YRE contributed
equally to this work and share first authorship. ZGQ, YXX, and MLL participatedin clinical care, recorded clinical data and diagnosed the patients. All authors
approved the final version of the manuscript.
Funding
All of the authors are employed by and receive a salary from ShanghaiChildren’s Medical Center affiliated to the Shanghai Jiaotong University Schoolof Medicine in China.
Data availability
The raw sequence data reported in this paper have been deposited in the
Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2021)
in National Genomics Data Center (Nucleic Acids Res 2022), China National
Center for Bioinformation / Beijing Institute of Genomics, Chinese AcademyMi et al. BMC Pediatrics(2024) 24:528

Page 5 of 6

of Sciences (GSA-Human: HRA006654) that are publicly accessible at https://
ngdc.cncb.ac.cn/gsa-human.

Declarations
Ethics approval and consent to participate
This research was approved by the Institutional Review Board of ShanghaiChildren’s Medical Center Affiliated to Shanghai Jiao Tong University School of
Medicine.
Consent for publication
Written informed consent was obtained from the parents of the patient topublish for personal or clinical details along with any identifying images to be
published in this study.
Competing interests
The authors declare no competing interests.

15.
16.

17.

18.
19.

Received: 5 May 2023 / Accepted: 7 February 2024
20.
References
1. Sun Y, Zhang J, Kraeft SK, Auclair D, Chang MS, Liu Y, Sutherland R, Salgia R,
Griffin JD, Ferland LH, et al. Molecular cloning and characterization of humantrabeculin-alpha, a giant protein defining a new family of actin-binding
proteins. J Biol Chem. 1999;274(47):33522–30.
2. Kang L, Liu Y, Jin Y, Li M, Song J, Zhang Y, Zhang Y, Yang Y. Mutations of
MACF1, encoding microtubule-actin crosslinking-factor 1, cause Spectraplakinopathy. Front Neurol. 2019;10:1335.
3. Jiang S, Yin C, Dang K, Zhang W, Huai Y, Qian A. Comprehensive ceRNA
network for MACF1 regulates osteoblast proliferation. BMC Genomics.
2022;23(1):695.
4. Wang P, Zhang J, Zhang H, Zhang F. The role of MACF1 on acute myeloid
leukemia cell proliferation is involved in Runx2-targeted PI3K/Akt signaling.
Mol Cell Biochem; 2022.
5. Tropeano M, Ahn JW, Dobson RJ, Breen G, Rucker J, Dixit A, Pal DK, McGuffin P, Farmer A, White PS, et al. Male-biased autosomal effect of 16p13.11
copy number variation in neurodevelopmental disorders. PLoS ONE.
2013;8(4):e61365.
6. Allach El Khattabi L, Heide S, Caberg JH, Andrieux J, Doco Fenzy M, VincentDelorme C, Callier P, Chantot-Bastaraud S, Afenjar A, Boute-Benejean O, et al.
16p13.11 microduplication in 45 new patients: refined clinical significanceand genotype-phenotype correlations. J Med Genet. 2020;57(5):301–7.
7. Williams NM, Zaharieva I, Martin A, Langley K, Mantripragada K, Fossdal R,
Stefansson H, Stefansson K, Magnusson P, Gudmundsson OO, et al. Rare
chromosomal deletions and duplications in attention-deficit hyperactivity
disorder: a genome-wide analysis. Lancet. 2010;376(9750):1401–8.
8. Ullmann R, Turner G, Kirchhoff M, Chen W, Tonge B, Rosenberg C, Field M,
Vianna-Morgante AM, Christie L, Krepischi-Santos AC, et al. Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism
and/or mental retardation. Hum Mutat. 2007;28(7):674–82.
9. Coe BP, Witherspoon K, Rosenfeld JA, van Bon BW, Vulto-van Silfhout AT,
Bosco P, Friend KL, Baker C, Buono S, Vissers LE, et al. Refining analyses of copy
number variation identifies specific genes associated with developmental
delay. Nat Genet. 2014;46(10):1063–71.
10. Kuang SQ, Guo DC, Prakash SK, McDonald ML, Johnson RJ, Wang M, Regalado
ES, Russell L, Cao JM, Kwartler C, et al. Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections. PLoS Genet. 2011;7(6):e1002118.
11. Cheng J, Novati G, Pan J, Bycroft C, Zemgulyte A, Applebaum T, Pritzel A, Wong LH, Zielinski M, Sargeant T, et al. Accurate proteome-wide
missense variant effect prediction with AlphaMissense. Science.
2023;381(6664):eadg7492.
12. Quang D, Chen Y, Xie X. DANN: a deep learning approach for annotating thepathogenicity of genetic variants. Bioinformatics. 2015;31(5):761–3.
13. Chen HJ, Lin CM, Lin CS, Perez-Olle R, Leung CL, Liem RK. The role of microtubule actin cross-linking factor 1 (MACF1) in the wnt signaling pathway. Genes
Dev. 2006;20(14):1933–45.
14. Dobyns WB, Aldinger KA, Ishak GE, Mirzaa GM, Timms AE, Grout ME,
Dremmen MHG, Schot R, Vandervore L, van Slegtenhorst MA, et al. MACF1

21.
22.
23.
24.

25.
26.
27.
28.
29.

30.

31.
32.
33.

mutations encoding highly conserved zinc-binding residues of the GAR
Domain cause defects in neuronal Migration and Axon Guidance. Am J Hum
Genet. 2018;103(6):1009–21.
Ka M, Kim WY. Microtubule-actin crosslinking factor 1 is required for dendritic
arborization and Axon Outgrowth in the developing brain. Mol Neurobiol.
2016;53(9):6018–32.
Cox AJ, Grady F, Velez G, Mahajan VB, Ferguson PJ, Kitchen A, Darbro BW,
Bassuk AG. In trans variant calling reveals enrichment for compound heterozygous variants in genes involved in neuronal development and growth.
Genet Res (Camb). 2019;101:e8.
Oury J, Liu Y, Topf A, Todorovic S, Hoedt E, Preethish-Kumar V, Neubert TA,
Lin W, Lochmuller H, Burden SJ. MACF1 links Rapsyn to microtubule- andactin-binding proteins to maintain neuromuscular synapses. J Cell Biol.
2019;218(5):1686–705.
Yang W, Zhao P, Cao P, Miao C, Ji X, Gao Y, Li P, Cheng J. Global interpretationof novel alternative splicing events in human congenital pulmonary airway
malformations: a pilot study. J Cell Biochem. 2022;123(4):736–45.
Irahara K, Saito Y, Sugai K, Nakagawa E, Saito T, Komaki H, Nakata Y, Sato N,
Baba K, Yamamoto T, et al. Pontine malformation, undecussated pyramidal tracts, and regional polymicrogyria: a new syndrome. Pediatr Neurol.
2014;50(4):384–8.
May-Simera HL, Gumerson JD, Gao C, Campos M, Cologna SM, Beyer T, Boldt
K, Kaya KD, Patel N, Kretschmer F, et al. Loss of MACF1 abolishes ciliogenesis and disrupts apicobasal polarity establishment in the Retina. Cell Rep.
2016;17(5):1399–413.
Su P, Tian Y, Yin C, Wang X, Li D, Yang C, Pei J, Deng X, King S, Li Y, et al. MACF1
promotes osteoblastic cell migration by regulating MAP1B through the
GSK3beta/TCF7 pathway. Bone. 2022;154:116238.
Fan D, Yang Y, Zhang W. A novel circ_MACF1/miR-942-5p/TGFBR2 axis
regulates the functional behaviors and drug sensitivity in gefitinib-resistantnon-small cell lung cancer cells. BMC Pulm Med. 2022;22(1):27.
Zhang Y, Ma Z, Li C, Wang C, Jiang W, Chang J, Han S, Lu Z, Shao Z, Wang Y, etal. The genomic landscape of cholangiocarcinoma reveals the disruption of
post-transcriptional modifiers. Nat Commun. 2022;13(1):3061.
Hannes FD, Sharp AJ, Mefford HC, de Ravel T, Ruivenkamp CA, Breuning MH,
Fryns JP, Devriendt K, Van Buggenhout G, Vogels A, et al. Recurrent reciprocal
deletions and duplications of 16p13.11: the deletion is a risk factor for MR/
MCA while the duplication may be a rare benign variant. J Med Genet.
2009;46(4):223–32.
Fujitani M, Zhang S, Fujiki R, Fujihara Y, Yamashita T. A chromosome 16p13.11
microduplication causes hyperactivity through dysregulation of miR-484/
protocadherin-19 signaling. Mol Psychiatry. 2017;22(3):364–74.
Ramalingam A, Zhou XG, Fiedler SD, Brawner SJ, Joyce JM, Liu HY, Yu S.
16p13.11 duplication is a risk factor for a wide spectrum of neuropsychiatricdisorders. J Hum Genet. 2011;56(7):541–4.
Nagamani SC, Erez A, Bader P, Lalani SR, Scott DA, Scaglia F, Plon SE, Tsai CH,
Reimschisel T, Roeder E, et al. Phenotypic manifestations of copy number
variation in chromosome 16p13.11. Eur J Hum Genet. 2011;19(3):280–6.
Arslan AB, Zamani AG, Yildirim MS. Novel findings, mini-review and dysmorphological characterization of 16p13.11 microduplication syndrome. Int J
Dev Neurosci. 2022;82(4):289–94.
Houcinat N, Llanas B, Moutton S, Toutain J, Cailley D, Arveiler B, Combe
C, Lacombe D, Rooryck C. Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in
two siblings born from consanguineous parents. Am J Med Genet A.
2015;167A(11):2714–9.
Salehi Karlslatt K, Pettersson M, Jantti N, Szafranski P, Wester T, Husberg B,
Ullberg U, Stankiewicz P, Nordgren A, Lundin J, et al. Rare copy number variants contribute pathogenic alleles in patients with intestinal malrotation. Mol
Genet Genomic Med. 2019;7(3):e549.
Redaelli S, Maitz S, Crosti F, Sala E, Villa N, Spaccini L, Selicorni A, Rigoldi M,
Conconi D, Dalpra L et al. Refining the phenotype of recurrent rearrangements of chromosome 16. Int J Mol Sci 2019, 20(5).
Serra G, Antona V, Schierz M, Vecchio D, Piro E, Corsello G. Esophageal atresia
and Beckwith-Wiedemann syndrome in one of the naturally conceived
discordant newborn twins: first report. Clin Case Rep. 2018;6(2):399–401.
Serra G, Antona V, Cimador M, Collodoro G, Guida M, Piro E, Schierz IAM,
Verde V, Giuffre M, Corsello G. New insights on partial trisomy 3q syndrome:de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception. Ital J Pediatr. 2023;49(1):17.

Mi et al. BMC Pediatrics(2024) 24:528

34. Serra G, Memo L, Antona V, Corsello G, Favero V, Lago P, Giuffre M. Jacobsen
syndrome and neonatal bleeding: report on two unrelated patients. Ital J
Pediatr. 2021;47(1):147.
35. Yan X, Li F, Liang Y, Shen Y, Zhao X, Huang Q, Zhu X. Human nudel and NudE
as regulators of cytoplasmic dynein in poleward protein transport along themitotic spindle. Mol Cell Biol. 2003;23(4):1239–50.
36. Houlihan SL, Feng Y. The scaffold protein Nde1 safeguards the brain genome
during S phase of early neural progenitor differentiation. Elife. 2014;3:e03297.
37. Brownstein CA, Kleiman RJ, Engle EC, Towne MC, D’Angelo EJ, Yu TW, Beggs
AH, Picker J, Fogler JM, Carroll D, et al. Overlapping 16p13.11 deletion andgain of copies variations associated with childhood onset psychosis include
genes with mechanistic implications for autism associated pathways: twocase reports. Am J Med Genet A. 2016;170A(5):1165–73.
38. Bradshaw NJ, Ukkola-Vuoti L, Pankakoski M, Zheutlin AB, Ortega-Alonso A,
Torniainen-Holm M, Sinha V, Therman S, Paunio T, Suvisaari J et al. The NDE1
genomic locus can affect treatment of psychiatric illness through gene
expression changes related to microRNA-484. Open Biol 2017, 7(11).
39. Zhu L, Vranckx R, Van Khau P, Lalande A, Boisset N, Mathieu F, Wegman M,
Glancy L, Gasc JM, Brunotte F, et al. Mutations in myosin heavy chain 11

Page 6 of 6

cause a syndrome associating thoracic aortic aneurysm/aortic dissection andpatent ductus arteriosus. Nat Genet. 2006;38(3):343–9.
40. Vysotskiy M, Zhong X, Miller-Fleming TW, Zhou D, Autism Working Group of
the Psychiatric Genomics C, Bipolar Disorder Working Group of the Psychiatric Genomics C, Schizophrenia Working Group of the Psychiatric, Genomics C, Cox NJ, Weiss LA. Integration of genetic, transcriptomic, and clinicaldata provides insight into 16p11.2 and 22q11.2 CNV genes. Genome Med.
2021;13(1):172.
41. Zhang J, Tang J, Li G, Li N, Wang J, Yao R, Yu T. SINE-VNTR-Alu retrotransposon
insertion as a novel mutational event underlying Glanzmann Thrombasthenia. J Thromb Haemost. 2023;21(12):3597–607.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.