Repository of Research and Investigative Information

Repository of Research and Investigative Information

Ilam University of Medical Sciences

A Novel Missense Mutation in the TGF-beta-binding Protein-Like Domain 3 of FBN1 Causes Weill-Marchesani Syndrome with Intellectual Disability

Mon Feb 26 04:21:59 2024

(2023) A Novel Missense Mutation in the TGF-beta-binding Protein-Like Domain 3 of FBN1 Causes Weill-Marchesani Syndrome with Intellectual Disability. Advanced Biomedical Research. p. 114. ISSN 2277-9175 (Print) 2277-9175 (Electronic) 2277-9175 (Linking)

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/37288014

Abstract

BACKGROUND: Weill-Marchesani syndrome (WMS) is a rare connective tissue disorder characterized by locus heterogeneity and variable expressivity. Patients suffering from WMS are described by short stature, brachydactyly, joint stiffness, congenital heart defects, and eye abnormalities. This disorder is inherited in two different modes; the autosomal dominant form of the disease occurs due to a mutation in FBN1, and the recessive form results from mutations in ADAMTS10, ADAMTS17, or LTP2 genes. MATERIALS AND METHODS: The family recruited in this study was a consanguineous Iranian family with an intellectually disabled girl referred to the Sadra Genetics laboratory, Shahrekord, Iran. The clinical history of family members was investigated. Whole-Exome Sequencing (WES) for the proband was performed. Sanger sequencing was used to assess the segregation of candidate variants in the other family members. RESULTS: Whole-exome sequencing analysis revealed a novel heterozygote mutation in the proband located at the third TGF-beta-binding protein-like (TB) domain of the FBN1 gene (NM000138: c.2066A>G: (p. Glu689Gly), NP000129.3, in exon 17 of the gene). Co-segregation analysis with Sanger sequencing confirmed this mutation in the affected members of the pedigree. CONCLUSION: Our findings represent an autosomal dominant form of specific WMS resulting from a substitution mutation in the FBN1 gene. In addition to the typical manifestations of the disorder, mild intellectual disability (ID) was identified in the 8-year-old proband. Given the fact that ID is primarily reported in ADAMTS10 mutated cases, this family was clinically and genetically a novel case.

Item Type: Article
Creators:
CreatorsEmail
Hassani, M.UNSPECIFIED
Taghizadeh, S.UNSPECIFIED
Farahzad Broujeni, A.UNSPECIFIED
Habibi, M.UNSPECIFIED
Banitalebi, S.UNSPECIFIED
Kasiri, M.UNSPECIFIED
Sadeghi, A.UNSPECIFIED
Nozari, A.UNSPECIFIED
Keywords: Fbn1 Weill-Marchesani syndrome intellectual disability whole-exome sequencing
Divisions:
Page Range: p. 114
Journal or Publication Title: Advanced Biomedical Research
Journal Index: Pubmed
Volume: 12
Identification Number: https://doi.org/10.4103/abr.abr₁₃₈₂₂
ISSN: 2277-9175 (Print) 2277-9175 (Electronic) 2277-9175 (Linking)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.medilam.ac.ir/id/eprint/4510

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