ABSTRACT
Myopathies and mitochondrial diseases pose a major challenge in diagnosis due to the multitude of different entities and - in the case of mitochondriopathies - the possible involvement of multiple organs. Furthermore, there is broad clinical variability within particular diseases; patients with hereditary myopathy, for example, can show great phenotypic variability despite identical genetic defects. In addition to environmental factors, gender-specific influences, and the degree of heteroplasmy in mitochondrial diseases, the existence of disease-modifying genes has long been assumed as an explanation. In recent years, risk genes, which can influence the course of disease, have been identified for some myopathies and mitochondrial diseases. The precise role of these disease-modifying genes in the pathogenesis of the diseases is largely unexplained and requires further research.
Subject(s)
Mitochondrial Diseases/genetics , Muscular Diseases/genetics , Diagnosis, Differential , Friedreich Ataxia/diagnosis , Friedreich Ataxia/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Mitochondrial Diseases/diagnosis , Muscular Diseases/diagnosis , Muscular Dystrophies/diagnosis , Muscular Dystrophies/genetics , Optic Atrophy, Hereditary, Leber/diagnosis , Optic Atrophy, Hereditary, Leber/genetics , PhenotypeABSTRACT
BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of inherited peripheral motor and sensory neuropathies with several modes of inheritance: autosomal dominant, X-linked, and autosomal recessive (AR) CMT. A locus responsible for the demyelinating form of ARCMT was assigned to the 5q23-q33 region (CMT4C) by homozygosity mapping. Recently, 11 mutations were identified in the SH3TC2 (KIAA1985) gene in 12 families with demyelinating ARCMT from Turkish, Iranian, Greek, Italian, or German origin. OBJECTIVE: To identify mutations in the SH3TC2 gene. METHODS: The authors searched for SH3TC2 gene mutations in 10 consanguineous CMT families putatively linked to the CMT4C locus on the basis of haplotype segregation and linkage analysis. RESULTS: Ten families had mutations, eight of which were new and one, R954X, recurrent. Six of the 10 mutations were in exon 11. Onset occurred between ages 2 and 10. Scoliosis or kyphoscoliosis and foot deformities were found in almost all patients and were often inaugural. The median motor nerve conduction velocity values (
