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Karger Publishers, Molecular Syndromology, 5(5), p. 218-228, 2014

DOI: 10.1159/000365057

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Exome Sequencing Identifies a DominantTNNT3Mutation in a Large Family with Distal Arthrogryposis

Journal article published in 2014 by Sarah B. Daly, Hitesh Shah, James O'Sullivan, Beverley Anderson, Sanjeev Bhaskar, Simon Williams, Nada Al-Sheqaih, Abdul Mueed Bidchol, Siddharth Banka ORCID, William G. Newman, Katta M. Girisha
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in <i>TNNT3 </i>in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability<i>. </i>This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders.