bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC‐C loci
Authors: Garavelli Livia , Piemontese Maria Rosaria , Cavazza Alberto , Rosato Simonetta , Wischmeijer Anita , Gelmini Chiara , Albertini Enrico , Albertini Giuseppe , Forzano Francesca , Franchi Fabrizia , Carella Massimo , Zelante Leopoldo , Superti‐Furga Andrea 
Published: October 2013

ABSTRACTGorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro‐ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS. © 2013 Wiley Periodicals, Inc.
Sensenbrenner syndrome (Cranioectodermal dysplasia): Clinical and molecular analyses of 39 patients including two new patients
Authors: Lin Angela E. , Traum Avram Z. , Sahai Inderneel , Keppler‐Noreuil Kim , Kukolich Mary K. , Adam Margaret P. , Westra Sjirk J. , Arts Heleen H. 
Published: October 2013

ABSTRACTSensenbrenner syndrome, also known as cranioectodermal dysplasia, is a rare multiple anomaly syndrome with distinctive craniofacial appearance, skeletal, ectodermal, connective tissue, renal, and liver anomalies. Dramatic advances with next‐generation sequencing have expanded its phenotypic variability and molecular heterogeneity. We review 39 patients including two new patients, one with compound heterozygous novel mutations in WDR35 and a previously unreported multisutural craniosynostosis that may be a part of Sensenbrenner syndrome. In 14 of 25 (56.0%) patients pathogenic mutations have been identified in 4 different genes that regulate (intraflagellar) cilia transport. We compared Sensenbrenner syndrome to asphyxiating thoracic dystrophy‐Jeune syndrome (ATD‐JS) and other ciliopathies. Our analyses showed that the high anterior hairline, forehead bossing and dolichocephaly (accompanied by sagittal craniosynostosis in more than half of the patients) occur in almost all patients with Sensenbrenner syndrome. Metaphyseal dysplasia with narrow thorax, proximal limb shortness, and short fingers are typical of Sensenbrenner syndrome and ATD‐JS. Respiratory complications have been reported in both syndromes, usually less severe with Sensenbrenner syndrome. Proposed diagnostic criteria for Sensenbrenner syndrome include the distinctive craniofacial appearance, ubiquitous brachydactyly and ectodermal anomalies, and sagittal craniosynostosis. Mild heart defects have been noted, but there have been no atrioventricular canal or heterotaxy defects that are common in Ellis‐Van Creveld syndrome. We anticipate that the steady identification of molecularly defined patients may allow correlation of phenotype and genotype. Additional natural history data will improve genetic counseling and current guidelines. © 2013 Wiley Periodicals, Inc.
PTEN hamartoma tumor syndromes in childhood: Description of two cases and a proposal for follow‐up protocol
Authors: Piccione Maria , Fragapane Tiziana , Antona Vincenzo , Giachino Daniela , Cupido Francesco , Corsello Giovanni 
Published: October 2013

ABSTRACTPTEN hamartoma tumor syndromes (PHTS) are a spectrum of hamartomatous overgrowth syndromes associated with germ‐line mutations in the tumor suppressor PTEN gene located on 10q23.3. It is widely accepted that two of these disorders, Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome, are allelic conditions. Because PTEN mutations are not identifiable in every case of the PHTS phenotype, the inability to detect a mutation within the PTEN gene does not invalidate the clinical diagnosis of Cowden syndrome, or Bannayan–Riley–Ruvalcaba syndrome, in patients who meet diagnostic criteria for these disorders. PTEN mutations are associated with an increased risk for developing breast, thyroid, endometrial, and sometimes renal cancers. Thus, cancer surveillance is the cornerstone of PHTS patient management. Although a consensus cancer surveillance protocol has not been formally instituted, all PTEN mutation carriers should adopt the cancer surveillance strategies proposed for patients with Cowden syndrome. In addition, because gastrointestinal and vascular complications can be more severe in Bannayan–Riley–Ruvalcaba syndrome than in Cowden syndrome, patients with Bannayan–Riley–Ruvalcaba syndrome should be monitored from this point of view too. In this study, we report on two cases with Bannayan–Riley–Ruvalcaba phenotype that showed two different PTEN mutations. We also propose practice recommendations for management of PHTS patients. © 2013 Wiley Periodicals, Inc.
Association study of 83 candidate genes for bipolar disorder in chromosome 6q selected using an evidence‐based prioritization algorithm
Authors: Bigdeli T. Bernard , Maher Brion S. , Zhao Zhongming , Sun Jingchun , Medeiros Helena , Akula Nirmala , McMahon Francis J. , Carvalho Celia , Ferreira Susana R. , Azevedo Maria H. , Knowles James A. , Pato Michele T. , Pato Carlos N. , Fanous Ayman H. 
Published: October 2013

AbstractBackgroundPrior genome‐scans of bipolar disorder have revealed chromosome 6q22 as a promising candidate region. However, linkage disequilibrium (LD) mapping studies have yet to identify replicated susceptibility loci.MethodsWe analyzed 1,422 LD‐tagging single nucleotide polymorphisms (SNPs) in 83 genes to test single‐marker and locus‐wide evidence of association with bipolar disorder in the NIMH Genetics Initiative bipolar pedigrees and the Portuguese Island Collection (PIC) (N = 1,093 in 528 informative pairs). Both studies previously demonstrated significant evidence of linkage to 6q. SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Evidence of single‐marker association was assessed using the generalized disequilibrium test (GDT). Empirical estimates of gene‐wide significance were obtained by permutation (via 100,000 gene‐dropping simulations) of Fisher's combined test of P‐values for each locus.ResultsNo single variant yielded significant experiment‐wide evidence of association, for either the combined sample or in each subsample. Our gene‐dropping simulations identified nominally significant gene‐wide associations with multiple loci, of which NT5DC1 in the NIMH subsample and CCNC in the PIC were the strongest candidates. However, no one gene consistently exceeded empirical significance criteria in both independent samples or survived Bonferroni correction for the number of genes tested.ConclusionsUsing a gene‐based approach to family‐based association, we identified gene‐wide associations with several genes, though no single locus was significantly associated with bipolar disorder in both cohorts. This suggests that chromosome 6q may harbor multiple susceptibility loci or that complex patterns of LD in this region may confound approaches based on common SNPs. Published 2013. This article is a U.S. Government work and is in the public domain in the USA
Effects of neuregulin‐1 genetic variation and depression symptom severity on longitudinal patterns of psychotic symptoms in primary care attendees
Authors: Bousman C.A. , Potiriadis M. , Everall I.P. , Gunn J.M. 
Published: October 2013

AbstractA better understanding of the factors associated with psychotic symptoms could aid early identification and treatment of psychotic disorders. Previous studies have typically utilized cross‐sectional study designs and have focused on individuals with psychotic disorders. Thus, examination of promising correlates of psychotic symptoms using longitudinal designs among more broadly defined populations is warranted. Two such correlates are neuregulin‐1 (NRG1) genotypic variation and depression symptom severity. Both NRG1 and depression symptom severity have cross‐sectional evidence for an association with psychosis but their affect on longitudinal patterns of psychotic symptoms and their potential interaction effects are less clear. Using repeated measures analysis of variance and covariance we modeled the main and interaction effects of NRG1 genotypic variation and depressive symptom severity on longitudinal psychotic symptom patterns in 301 primary care attendees assessed annually over 4 years. One‐fifth (19.9%) of the participants reported one or more psychotic symptoms over the 4‐year assessment period. We observed a curvilinear (i.e., cubic) association between depression symptom severity at baseline and longitudinal patterns of psychotic symptoms but did not observe a main effect for NRG1 genotypic variation on psychotic symptom patterns. However, NRG1 rs6994992 genotype moderated the curvilinear association between depression symptom severity and psychotic symptom patterns. Specifically, depression symptom severity had less of an effect on longitudinal psychotic symptoms among carriers of the rs6994992 TT genotype compared to CC and CT carriers. Our findings suggest a curvilinear association between depression symptom severity and longitudinal patterns of psychotic symptoms that is moderated by NRG1 genotype. © 2013 Wiley Periodicals, Inc.
How might ZNF804A variants influence risk for schizophrenia and bipolar disorder? A literature review, synthesis, and bioinformatic analysis
Authors: Hess Jonathan L. , Glatt Stephen J. 
Published: October 2013

AbstractThe gene that encodes zinc finger protein 804A (ZNF804A) became a candidate risk gene for schizophrenia (SZ) after surpassing genome‐wide significance thresholds in replicated genome‐wide association scans and meta‐analyses. Much remains unknown about this reported gene expression regulator; however, preliminary work has yielded insights into functional and biological effects of ZNF804A by targeting its regulatory activities in vitro and by characterizing allele‐specific interactions with its risk‐conferring single nucleotide polymorphisms (SNPs). There is now strong epidemiologic evidence for a role of ZNF804A polymorphisms in both SZ and bipolar disorder (BD); however, functional links between implicated variants and susceptible biological states have not been solidified. Here we briefly review the genetic evidence implicating ZNF804A polymorphisms as genetic risk factors for both SZ and BD, and discuss the potential functional consequences of these variants on the regulation of ZNF804A and its downstream targets. Empirical work and predictive bioinformatic analyses of the alternate alleles of the two most strongly implicated ZNF804A polymorphisms suggest they might alter the affinity of the gene sequence for DNA‐ and/or RNA‐binding proteins, which might in turn alter expression levels of the gene or particular ZNF804A isoforms. Future work should focus on clarifying the critical periods and cofactors regulating these genetic influences on ZNF804A expression, as well as the downstream biological consequences of an imbalance in the expression of ZNF804A and its various mRNA isoforms. © 2013 Wiley Periodicals, Inc.
Facial dysostoses: Etiology, pathogenesis and management
Authors: Trainor Paul A. , Andrews Brian T. 
Published: October 2013

AbstractApproximately 1% of all live births exhibit a minor or major congenital anomaly. Of these approximately one‐third display craniofacial abnormalities which are a significant cause of infant mortality and dramatically affect national health care budgets. To date, more than 700 distinct craniofacial syndromes have been described and in this review, we discuss the etiology, pathogenesis and management of facial dysostoses with a particular emphasis on Treacher Collins, Nager and Miller syndromes. As we continue to develop and improve medical and surgical care for the management of individual conditions, it is essential at the same time to better characterize their etiology and pathogenesis. Here we describe recent advances in our understanding of the development of facial dysostosis with a view towards early in utero identification and intervention which could minimize the manifestation of anomalies prior to birth. The ultimate management for any craniofacial anomaly however, would be prevention and we discuss this possibility in relation to facial dysostosis. © 2013 Wiley Periodicals, Inc.
The ontology of craniofacial development and malformation for translational craniofacial research
Authors: Brinkley J.F. , Borromeo C. , Clarkson M. , Cox T.C. , Cunningham M.J. , Detwiler L.T. , Heike C.L. , Hochheiser H. , Mejino J.L.V. , Travillian R.S. , Shapiro L.G. 
Published: October 2013

AbstractWe introduce the Ontology of Craniofacial Development and Malformation (OCDM) as a mechanism for representing knowledge about craniofacial development and malformation, and for using that knowledge to facilitate integrating craniofacial data obtained via multiple techniques from multiple labs and at multiple levels of granularity. The OCDM is a project of the NIDCR‐sponsored FaceBase Consortium, whose goal is to promote and enable research into the genetic and epigenetic causes of specific craniofacial abnormalities through the provision of publicly accessible, integrated craniofacial data. However, the OCDM should be usable for integrating any web‐accessible craniofacial data, not just those data available through FaceBase. The OCDM is based on the Foundational Model of Anatomy (FMA), our comprehensive ontology of canonical human adult anatomy, and includes modules to represent adult and developmental craniofacial anatomy in both human and mouse, mappings between homologous structures in human and mouse, and associated malformations. We describe these modules, as well as prototype uses of the OCDM for integrating craniofacial data. By using the terms from the OCDM to annotate data, and by combining queries over the ontology with those over annotated data, it becomes possible to create “intelligent” queries that can, for example, find gene expression data obtained from mouse structures that are precursors to homologous human structures involved in malformations such as cleft lip. We suggest that the OCDM can be useful not only for integrating craniofacial data, but also for expressing new knowledge gained from analyzing the integrated data © 2013 Wiley Periodicals, Inc.
Modeling anterior development in mice: Diet as modulator of risk for neural tube defects
Authors: Kappen Claudia 
Published: October 2013

AbstractHead morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient–gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. © 2013 Wiley Periodicals, Inc.
Genetics of cleft lip and cleft palate
Authors: Leslie Elizabeth J. , Marazita Mary L. 
Published: October 2013

AbstractOrofacial clefts are common birth defects and can occur as isolated, nonsyndromic events or as part of Mendelian syndromes. There is substantial phenotypic diversity in individuals with these birth defects and their family members: from subclinical phenotypes to associated syndromic features that is mirrored by the many genes that contribute to the etiology of these disorders. Identification of these genes and loci has been the result of decades of research using multiple genetic approaches. Significant progress has been made recently due to advances in sequencing and genotyping technologies, primarily through the use of whole exome sequencing and genome‐wide association studies. Future progress will hinge on identifying functional variants, investigation of pathway and other interactions, and inclusion of phenotypic and ethnic diversity in studies. © 2013 Wiley Periodicals, Inc.
Chiral‐Amine‐Catalyzed Asymmetric Bromocyclization of Tryptamine Derivatives
Authors: Cai Quan , Yin Qin , You Shu‐Li 
Published: October 2013

AbstractChiral hexahydropyrro[2,3]indole (HPI) units exist widely in natural and unnatural products with significant biological activities. The enantioselective synthesis of brominated hexahydropyrrolo[2,3‐b]indole (HPI) subunits by asymmetric bromocyclization of tryptamine derivatives catalyzed by a chiral amine has been realized. In the presence of hydroquinine 1,4‐phthalazinediyl diether ((DHQ)2PHAL, 20 mol %) and L‐(‐)‐camphorsulfonic acid (20 mol %), enantioenriched brominated HPI derivatives were obtained from readily available substituted tryptamines in up to 99% yield and 73% ee.
Genetic affinities of Ukrainians from the maternal perspective
Authors: Pshenichnov Andrey , Balanovsky Oleg , Utevska Olga , Metspalu Ene , Zaporozhchenko Valery , Agdzhoyan Anastasia , Churnosov Mikhail , Atramentova Lyubov , Balanovska Elena 
Published: October 2013

ABSTRACTThe area of what is now the Ukraine has been the arena of large‐scale demographic processes that may have left their traces in the contemporary gene pool of Ukrainians. In this study, we present new mitochondrial DNA data for 607 Ukrainians (hypervariable segment I sequences and coding region polymorphisms). To study the maternal affinities of Ukrainians at the level of separate mitochondrial haplotypes, we apply an original technique, the haplotype co‐occurrence analysis. About 20% of the Ukrainian maternal gene pool is represented by lineages highly specific to Ukrainians, but is scarcely found in other populations. About 9% of Ukrainian mtDNA lineages are typical for peoples of the Volga region. We also identified minor gene pool strata (1.6–3.3%), each of which is common in Lithuanians, Estonians, Saami, Nenets, Cornish, and the populations of the North Caucasus. Am J Phys Anthropol 152:543–550, 2013. © 2013 Wiley Periodicals, Inc.
An investigation of ecological correlates with hand and foot morphology in callitrichid primates
Authors: Smith Joanna M. , Smith Andrew C. 
Published: October 2013

ABSTRACTStudies of primate taxonomy and phylogeny often depend on comparisons of limb dimensions, yet there is little information on how morphology correlates and contributes to foraging strategies and ecology. Callitrichid primates are ideal for comparative studies as they exhibit a range of body size, limb proportions and diet. Many callitrichid species exhibit a high degree of exudativory, and to efficiently exploit these resources, they are assumed to have evolved morphologies that reflect a level of dependence on these resources. We tested assumptions by considering measurements of limb proportion and frictional features of the volar surfaces in preserved specimens of 25 species with relation to published life history and ecological data. The degree of exudativory and utilization of vertical substrates during foraging were found to correlate both with size and with size‐corrected foot and hand dimensions. Smaller species, which engage in greater degrees of exudativory, had proportionally longer hands and feet and more curved claw‐like tegulae (nails) on their digits to facilitate climbing on vertical substrates. The density of patterned ridges (dermatoglyphs) on the volar surfaces of the hands and feet is higher in more exudativorous genera, suggesting a role in climbing on vertical tree trunks during foraging. Dermatoglyph comparisons suggest that ridges on the soles and palms may facilitate food procurement by enhancing frictional grip during exudate feeding. Volar pad features corroborate taxonomic relationships described from dental morphology. Am J Phys Anthropol 152:447–458, 2013. © 2013 Wiley Periodicals, Inc.
Epistaxis: the factors involved in determining medicolegal liability
Authors: Khan Mohemmed N. , Blake Danielle M. , Vazquez Alejandro , Setzen Michael , Baredes Soly , Eloy Jean Anderson 
Published: October 2013

BackgroundThe purpose of this study was to examine litigation involving epistaxis and analyze factors that determine liability.MethodsJury verdicts and settlements regarding cases involving epistaxis were gathered utilizing the Westlaw database. Factors involved in litigation gathered included demographics, defendant specialty, procedure, alleged cause of malpractice, outcome, monetary award, and other variables.ResultsA total of 26 cases were analyzed. The majority of cases (57.7%) were decided in favor of the plaintiff or settled out of court. Total awards amounted to $24,501,252. Average awards for cases decided in favor of the plaintiff were $2,260,893 and ranged from $499,845 to $9,022,643. Settlements averaged $1,084,375 and ranged from $300,000 to $3,800,000. Common causes of malpractice encountered included delay in diagnosis, complications from medical procedures, and failure to recognize complications in a timely manner.ConclusionContrary to previous reports analyzing malpractice for varying medical procedures and complications, litigation in epistaxis is more commonly resolved in favor of the plaintiff or resolved through out‐of‐court settlements. Substantial financial awards and therapeutic complications from blindness to death make epistaxis a candidate for litigation. Of importance from a medicolegal stand is the fact that 30.8% (8) of the patients involved in epistaxis litigation died, either from complications of therapy or from experiencing epistaxis as a complication of another procedure/pathology. Using necessary diagnostic imaging, ensuring proper management techniques, and recognizing complications in a timely manner can serve to limit legal liability and enhance patient safety.