Report of Limb Girdle Muscular Dystrophy Type 2A in 6 Iranian Patients, One With a Novel Deletion in Capn3 Gene Publisher Pubmed



Fadaee M^{1, 2} ; Kariminejad A² ; Fattahi Z^{1, 2} ; Nafissi S³ ; Godarzi HR^{4, 7} ; Beheshtian M^{1, 2} ; Vazehan R² ; Akbari MR^{5, 6} ; Kahrizi K¹ ; Najmabadi H^{1, 2} Show Affiliations
Source: Neuromuscular Disorders Published:2016

Abstract

Calpain3 is a calcium-dependent intracellular protease involved in an autosomal recessive form of muscular dystrophy known as limb-girdle muscular dystrophy type 2A. Many pathogenic mutations have been identified in calpain3, encoded by the CAPN3 gene, which leads to weakness of the pelvic and shoulder girdle muscles. In the present study, whole exome sequencing was performed on six unrelated Iranian families who presented with progressive muscle weakness, with a strong suspicion of Calpainopathies. Genetic analysis of CAPN3 gene revealed five causative variants which had not been reported in the Iranian population before including a novel 6 bp deletion (c.795_800delCATTGA) and four previously reported mutations (c.1939G > T, c.2243G > A, c.2257delGinsAA, and c.2380 + 2T > G). Our findings indicate that exome sequencing can be a very effective and affordable method to diagnose heterogeneous muscular dystrophies, especially in consanguineous populations such as Iran. © 2016 Elsevier B.V.