Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel TFAP2A mutation in a Japanese family with Branchio-oculo-facial syndrome.

ABSTRACT: Branchio-oculo-facial syndrome (BOFS) is a rare autosomal dominant disorder characterized by craniofacial, ocular, and ectodermal anomalies. BOFS is caused by mutation of the transcription factor AP2-alpha gene (TFAP2A). We performed detailed genetic analysis of a Japanese family with clinically suspected BOFS and identified a novel missense mutation resulting in a predicted amino-acid substitution in the highly conserved basic DNA-binding domain of TFAP2A (NM_003220.2:c.699A>C).

SUBMITTER: Sato T

PROVIDER: S-EPMC5945586 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Novel TFAP2A mutation in a Japanese family with Branchio-oculo-facial syndrome.

Sato Taisuke T Samura Osamu O Kato Noriko N Taniguchi Kosuke K Takahashi Ken K Ito Yuki Y Aoki Hiroaki H Kobayashi Masahisa M Migita Ohsuke O Okamoto Aikou A Hata Kenichiro K

Human genome variation 20180510

Branchio-oculo-facial syndrome (BOFS) is a rare autosomal dominant disorder characterized by craniofacial, ocular, and ectodermal anomalies. BOFS is caused by mutation of the transcription factor AP2-alpha gene (TFAP2A). We performed detailed genetic analysis of a Japanese family with clinically suspected BOFS and identified a novel missense mutation resulting in a predicted amino-acid substitution in the highly conserved basic DNA-binding domain of TFAP2A (NM_003220.2:c.699A>C). ...[more]

PMID: 29760939

Similar Datasets

TFAP2A mutations result in branchio-oculo-facial syndrome.

Project description:Branchio-oculo-facial syndrome (BOFS) is a rare autosomal-dominant cleft palate-craniofacial disorder with variable expressivity. The major features include cutaneous anomalies (cervical, infra- and/or supra-auricular defects, often with dermal thymus), ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies. The molecular basis for this disorder is heretofore unknown. We detected a 3.2 Mb deletion by 500K SNP microarray in an affected mother and son with BOFS at chromosome 6p24.3. Candidate genes in this region were selected for sequencing on the basis of their expression patterns and involvement in developmental pathways associated with the clinical findings of BOFS. Four additional BOFS patients were found to have de novo missense mutations in the highly conserved exons 4 and 5 (basic region of the DNA binding domain) of the TFAP2A gene in the candidate deleted region. We conclude BOFS is caused by mutations involving TFAP2A. More patients need to be studied to determine possible genetic heterogeneity and to establish whether there are genotype-phenotype correlations.

| S-EPMC2427243 | biostudies-literature

A Heterozygous Novel Mutation in TFAP2A Gene Causes Atypical Branchio-Oculo-Facial Syndrome With Isolated Coloboma of Choroid: A Case Report.

Project description:Background: Branchio-oculo-facial syndrome (BOFS) is a rare congenital developmental disorder with highly variable clinical phenotypes in autosomal dominant inheritance. The aim of this study is to identify disease-causing mutations in a Chinese family with predominant coloboma of choroid. Case report: We described a family (a mother and her daughter) with unclear clinical diagnosis. The mother (proband) presented with bilateral coloboma of choroid, whereas her daughter had a relatively severe phenotype and presented with larger bilateral choroid coloboma and high-vaulted arch. We applied the next generation sequencing (NGS) panel and analyzed 776 genes related to inherited ocular disorders on the proband. Four candidate heterozygous variants in four genes, respectively, were detected in the proband. Validation of these variants were subsequently performed in the family using Sanger sequencing. Among these variants, a novel nonsense mutation c.912C>A, p.(Cys304*) (NM_001042425.2) which in exon 6 of the conserved helix-span-helix domain in TFAP2A results in a premature termination codon. It may trigger nonsense-mediated mRNA decay (NMD). Both the affected mother and daughter had this variant, whereas it was absent in the asymptomatic father. Together with the silicon tools and clinical features, we concluded that the variant c.912C>A, p.(Cys304*), was the second reported nonsense mutation in TFAP2A gene, which was the disease-causing mutation of the family. Conclusion: There are many hereditary diseases accompanied by ocular anomalies. For instance, BOFS, patients with atypical features are always at risk of being under-diagnosed. NGS is a powerful method to identify the genetic cause and improve genetic counseling for less clarified hereditary ocular diseases.

| S-EPMC7379893 | biostudies-literature

Analysis of TFAP2A mutations in Branchio-Oculo-Facial Syndrome indicates functional complexity within the AP-2α DNA-binding domain.

Project description:Multiple lines of evidence indicate that the AP-2 transcription factor family has an important regulatory function in human craniofacial development. Notably, mutations in TFAP2A, the gene encoding AP-2α, have been identified in patients with Branchio-Oculo-Facial Syndrome (BOFS). BOFS is an autosomal-dominant trait that commonly presents with facial clefting, eye defects and branchial skin anomalies. Examination of multiple cases has suggested either simple haploinsufficiency or more complex genetic causes for BOFS, especially as the clinical manifestations are variable, with no clear genotype-phenotype correlation. Mutations occur throughout TFAP2A, but mostly within conserved sequences within the DNA contact domain of AP-2α. However, the consequences of the various mutations for AP-2α protein function have not been evaluated. Therefore, it remains unclear if all BOFS mutations result in similar changes to the AP-2α protein or if they each produce specific alterations that underlie the spectrum of phenotypes. Here, we have investigated the molecular consequences of the mutations that localize to the DNA-binding region. We show that although individual mutations have different effects on DNA binding, they all demonstrate significantly reduced transcriptional activities. Moreover, all mutant derivatives have an altered nuclear:cytoplasmic distribution compared with the predominantly nuclear localization of wild-type AP-2α and several can exert a dominant-negative activity on the wild-type AP-2α protein. Overall, our data suggest that the individual TFAP2A BOFS mutations can generate null, hypomorphic or antimorphic alleles and that these differences in activity, combined with a role for AP-2α in epigenetic events, may influence the resultant pathology and the phenotypic variability.

| S-EPMC3723307 | biostudies-literature

Ocular manifestations of branchio-oculo-facial syndrome: report of a novel mutation and review of the literature.

Project description:PURPOSE: To report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A). METHODS: Full ophthalmological evaluation and direct sequencing of TFAP2A. RESULTS: A 10-year-old girl with unusual ocular manifestations of BOFS such as elliptical shaped microcornea and a novel de novo TFAP2A mutation was identified. CONCLUSIONS: This report expands the ocular phenotypic spectrum of BOFS and adds to the small number of reported TFAP2A mutations.

| S-EPMC2866573 | biostudies-literature

FOXD1 Duplication Causes Branchial Defects and Interacts with the TFAP2A Gene Implicated in the Branchio-Oculo-Facial Syndrome in Causing Eye Effects in Zebrafish.

Project description:Branchio-oculo-facial syndrome (BOFS) is a rare disorder characterized by maldevelopment of the first and second branchial arches, skin defects, facial dysmorphism, auricular, ophthalmological and oral abnormalities. A high clinical variability has been reported. Recently, mutations in TFAP2A were found to underlie this condition. A small duplication on 5q13 was detected in 2 family members with mild BOFS features. Molecular cytogenetic delineation of the duplication demonstrated that only 7 genes are affected: LOC100289045, RGNEF, UTP15, ANKRA2, FUNDC2P1, BTF3 and FOXD1. The latter is expressed in the developing branchial arches and involved in cranio-facial development. Zebrafish embryos with combined inhibition of the expression of foxd1l and tfap2a show optic axis defects. We identified a novel locus associated with a mild BOFS-like phenotype. The functional in vivo experiments suggest an interaction between FOXD1 and TFAP2A.

| S-EPMC3214949 | biostudies-literature

Disruption of the TFAP2A regulatory domain causes Branchio-Oculo-Facial Syndrome (BOFS) and illuminates pathomechanisms for other human neurocristopathies

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-01 | GSE108522 | GEO

Disruption of the TFAP2A regulatory domain causes Branchio-Oculo-Facial Syndrome (BOFS) and illuminates pathomechanisms for other human neurocristopathies [scRNA-seq]

Project description:BOFS is a rare congenital syndrome that arises due to defects during neural crest (NC) development and is thus considered as a human neurocristopathy. All reported BOFS cases are caused by heterozygous mutations within TFAP2A. Here we describe a unique BOFS patient carrying a de novo heterozygous inversion in which one of the breakpoints is located 40 kb downstream of TFAP2A. Using in vitro and in vivo NC developmental models, we uncovered that TFAP2A is located within a large Topologically Associating Domain (TAD) containing enhancers essential for TFAP2A expression in NC cells (NCC). Importantly, using patient-specific hiPSC lines, we showed that the inversion causes a loss of physical interactions between the inverted TFAP2A allele and its cognate enhancers, leading to TFAP2A monoallelic and haploinsufficient expression in human NCC. More generally, our results highlight potential etiological mechanisms for other human neurocristopathies and illustrate how TAD disruption can lead to a loss of enhancer gene-interactions and, consequently, to pathological changes in gene expression.

2018-11-01 | GSE121429 | GEO