Autosomal recessive Emery-Dreifuss muscular dystrophy caused by a novel mutation (R225Q) in the lamin A/C gene identified by exome sequencing

Introduction: The aim of this study is to describe a new mutation in the LMNA gene diagnosed by whole exome sequencing. Methods: A two‐generation kindred with recessive limb‐girdle muscular dystrophy was evaluated by exome sequencing of the proband's DNA. Results: Exome sequencing disclosed 194,618 variants (170,196 SNPs, 8482 MNPs, 7466 insertions, 8307 deletions, and 167 mixed combinations); 71,328 were homozygotic and 123,290 were heterozygotic, with 11,753 non‐synonymous, stop‐gain, stop‐loss, or frameshift mutations occurring in the coding region or nearby intronic region. The cross‐referencing of these mutations in candidate genes for muscular dystrophy showed a homozygote mutation c.G674A in exon 4 of LMNA causing a protein change R225Q in an arginine conserved from human to Xenopus tropicalis and in lamin B1. Conclusions: This technique will be preferred for studying patients with muscular dystrophy in the coming years. Muscle Nerve, 2012