TY - JOUR
T1 - Exome sequencing identifies a dominant tnnt3 mutation in a large family with distal arthrogryposis
AU - Daly, Sarah B.
AU - Shah, Hitesh
AU - O'Sullivan, James
AU - Anderson, Beverley
AU - Bhaskar, Sanjeev
AU - Williams, Simon
AU - Al-Sheqaih, Nada
AU - Mueed Bidchol, Abdul
AU - Banka, Siddharth
AU - Newman, William G.
AU - Girisha, Katta M.
PY - 2014
Y1 - 2014
N2 - 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 TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders.
AB - 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 TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders.
UR - http://www.scopus.com/inward/record.url?scp=84906886123&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906886123&partnerID=8YFLogxK
U2 - 10.1159/000365057
DO - 10.1159/000365057
M3 - Article
AN - SCOPUS:84906886123
SN - 1661-8769
VL - 5
SP - 218
EP - 228
JO - Molecular Syndromology
JF - Molecular Syndromology
IS - 5
ER -