3个意大利家族中与遗传性感觉运动神经病相关的新的GDAP1基因突变:奠基者效应的证据

A novel mutation of GDAP1 associated with Charcot Marie Tooth disease in three Italian families: Evidence for a founder effect

Background: Mutations in a gene encoding a novel protein of unknown function the ganglioside induced differentia tion associated protein 1 gene (GDAP1) are associated with the autosomal recessive Charcot Marie Tooth disease type 4A (CMT4A). Objective: To investigate the role of GDAP1 mutations in causing au tosomal recessive neuropathies in an Italian population. Methods and results: 76 patients with severe early onset polyneuropathy and possible autosomal recessiv e inheritance were screened for mutations. A T > G transversion (c.347 T > G) at codon 116 (M116R) was detected in four affected subjects from three apparently unrelated families. All patients had early onset of disease with pronounced foot deformities and impaired walking. Neurophysiological studies showed an extremel y variable expression. Sural nerve biopsies revealed signs of both de remyelina tion and axonal impairment, the most prominent feature being a severe loss of la rger fibres. Haplotype analysis of the GDAP1 locus demonstrated a common disease haplotype. Conclusions: The association of the mutation with a common haplotype suggested a common ancestor.