A novel mutation of GDAP1 associated with Charcot-Marie-Tooth disease in three Italian families: evidence for a founder effect
- E Di Maria1,
- R Gulli1,
- P Balestra1,
- D Cassandrini1,
- S Pigullo1,
- L Doria-Lamba2,
- M Bado3,
- A Schenone1,
- F Ajmar1,
- P Mandich1,
- E Bellone1
- 1Department of Neuroscience, Ophthalmology and Genetics, University of Genova, Genova, Italy
- 2U.O. e Cattedra di Neuropsichiatria Infantile, Institute “G Gaslini”, Genova
- 3Neuromuscular Diseases Unit, Department of Paediatrics, Institute “G Gaslini”
- Correspondence to: Dr E Bellone Department of Neuroscience, Ophthalmology and Genetics, Section of Medical Genetics, University of Genova, c/o DIMI – Viale Benedetto XV, 6 16132 Genova, Italy; ebelloneunige.it
- Received 16 September 2003
- Accepted 13 January 2004
- Revised 8 January 2004
Abstract
Background: Mutations in a gene encoding a novel protein of unknown function—the ganglioside-induced differentiation-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 autosomal recessive neuropathies in an Italian population.
Methods and results: 76 patients with severe early onset polyneuropathy and possible autosomal recessive 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 extremely variable expression. Sural nerve biopsies revealed signs of both de-remyelination and axonal impairment, the most prominent feature being a severe loss of larger 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.
- ARCMT, autosomal recessive Charcot-Marie-Tooth disease
- CMT, Charcot-Marie-Tooth disease
- GDAP1, ganglioside-induced differentiation-associated protein 1
Footnotes
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Competing interests: none declared
