Novel mutations in three patients with LGMD2C with phenotypic differences

Abstract

Limb-girdle muscular dystrophy type 2C is an autosomal-recessive disorder caused by mutations in gamma-sarcoglycan encoding gene. This disease is characterized by childhood onset of progressive muscular dystrophy. Because of the clinical presentation, this disorder may be misdiagnosed as a dystrophinopathy. Two males (Patients A and B) from one Turkish family and one male (Patient C) from a Moroccan family had progressive walking disturbances for several years, exercise intolerance, and leg pains. Clinical examination revealed limb-girdle weakness and calf hypertrophy. Serum creatine kinase levels ranged from 1100 to 19000 U/L. The initial findings and course of the disease were less severe in Patient B compared with his brother (Patient A) at the same age. By means of immunohistochemistry on muscle biopsy all patients manifested reduced expression of alpha-, beta-, gamma-, and delta-sarcoglycans. DNA sequence analysis revealed a homozygous splice site mutation in exon 5 (IVS5+2T>C) in the Turkish family. In the patient from the Moroccan family a homozygous nonsense mutation in exon 2 (93G>A;Trp31X) was present. In conclusion, this report describes the clinical, histologic, and immunohistochemical characteristics of three children with limb-girdle muscular dystrophy type 2C. Two novel mutations in the gamma-sarcoglycan gene were present. We found phenotypic differences in two brothers.