title: 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.
authors.affiliation: Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
authors.forename: Sascha
authors.initials: S
authors.lastname: Vermeer
authors.forename: Aad
authors.initials: A
authors.lastname: Verrips
authors.forename: Michèl A A P
authors.initials: MA
authors.lastname: Willemsen
authors.forename: Henk J
authors.initials: HJ
authors.lastname: ter Laak
authors.forename: Ieke B
authors.initials: IB
authors.lastname: Ginjaar
authors.forename: Ben C J
authors.initials: BC
authors.lastname: Hamel
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018389:Codon, Nonsense / Q000235:genetics*; D003241:Consanguinity; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D049030:Dystroglycans; D005091:Exons / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009460:Neurologic Examination; D010641:Phenotype
chemical_list: D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D049030:Dystroglycans