Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 65

Abstract

Mutations in a gene encoding a novel protein of unknown function, the ganglioside‐induced differentiation‐associated protein 1 gene (GDAP1), are associated with one of the autosomal recessive forms of Charcot‐Marie‐Tooth disease (CMT4A). Mutations in GDAP1 can cause both axonal and demyelinating inherited peripheral neuropathies. The GDAP1 gene maps on chromosome 8q21.1, encompassing 13.9 kb of genomic DNA. The coding sequence is comprised of six exons. Little is known about the function of GDAP1. The mouse homologue Gdap1 is highly expressed in brain. Northern‐blot analysis showed that GDAP1 is also expressed in peripheral nerves, both in neurons and in Schwann cells. A series of Italian patients with demyelinating (n = 42) and axonal (n = 39) peripheral neuropathy with possible recessive inheritance was screened for mutations in the GDAP1 gene. The entire coding region, including exon‐intron boundaries, was examined by single strand conformation polymorphism (SSCP) and direct sequencing. All patients were negative for the 17p11.2 duplication and for mutations in the MPZ, GJB1, PMP22 and EGR2 genes. SSCP analysis showed a few electrophoretic variants, in the exon 1, exon 3 and exon 4, respectively. Direct sequencing demonstrated the presence of a common single nucleotide polymorphism in the exon 4 (c.507T > G) and a nucleotide substitution in the exon 3. The latter was found in four patients, belonging to three families, and was not detected in a series of normal subjects. Further studies are in progress to evaluate the possible role of this variant in the pathophysiology of the disease. This work was partially supported by grants MURST 2000 to F.A. and Ministero della Sanità to P.M.