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

Abstract

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.

• Authors: Adriano Jimenez-Escrig, Isabel Gobernado, Mercedes Garcia-Villanueva, Antonio Sanchez-Herranz
• Journal: Muscle & nerve (Muscle Nerve) Vol. 45 Issue 4 Pg. 605-10 (Apr 2012) ISSN: 1097-4598 [Electronic] United States
• PMID: 22431096 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

• LMNA protein, human
• Lamin Type A
• Creatine Kinase

Topics

• Age of Onset
• Animals
• Biopsy
• Creatine Kinase (blood)
• Diplopia (etiology)
• Disease Progression
• Exome (genetics)
• Female
• Frameshift Mutation
• Gait Disorders, Neurologic (etiology)
• Heart Diseases (etiology)
• Humans
• Lamin Type A (genetics)
• Middle Aged
• Molecular Sequence Data
• Muscle, Skeletal (physiology)
• Muscular Dystrophy, Emery-Dreifuss (diagnosis, genetics, pathology)
• Mutation (genetics, physiology)
• Pedigree
• Sequence Analysis, DNA
• Xenopus (genetics)