Novel mutations in three patients with LGMD2C with phenotypic differences

Vermeer, Sascha; Verrips, Aad; Willemsen, Michèl A.A.P.; ter Laak, Henk J.; Ginjaar, Ieke B.; Hamel, Ben C.J.

doi:10.1016/j.pediatrneurol.2003.11.006

« Previous Next »Pediatric Neurology
Volume 30, Issue 4 , Pages 291-294, April 2004

Novel mutations in three patients with LGMD2C with phenotypic differences

Sascha Vermeer, MD
- Communications should be addressed to:Dr. Vermeer; Department of Human Genetics; University Medical Centre Nijmegen; P.O. Box 9101; 6500 HB Nijmegen;The Netherlands.
- Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Aad Verrips, MD, PhD
- Department of Pediatric Neurology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
- Department of Neurology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Michèl A.A.P. Willemsen, MD, PhD
- Department of Pediatric Neurology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Henk J. ter Laak, PhD
- Department of Neurology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Ieke B. Ginjaar, PhD
- Center of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
- Department of Pathology, University Medical Centre Nijmegen, Nijmegen, The Netherlands
Ben C.J. Hamel, MD, PhD
- Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands

Received 3 June 2003; accepted 10 November 2003.

Abstract

Limb-girdle muscular dystrophy type 2C is an autosomal-recessive disorder caused by mutations in γ-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 19,000 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 α-, β-, γ-, and δ-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 γ-sarcoglycan gene were present. We found phenotypic differences in two brothers.