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.
| Original language | English |
|---|---|
| Pages (from-to) | 1495-1498 |
| Number of pages | 4 |
| Journal | Journal of Neurology, Neurosurgery and Psychiatry |
| Volume | 75 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2004 |
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ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology
- Neuroscience(all)
- Psychiatry and Mental health
Cite this
A novel mutation of GDAP1 associated with Charcot-Marie-Tooth disease in three Italian families : Evidence for a founder effect. / Di Maria, E.; Gulli, R.; Balestra, P.; Cassandrini, D.; Pigullo, S.; Doria-Lamba, L.; Bado, M.; Schenone, A.; Ajmar, F.; Mandich, P.; Bellone, E.
In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 75, No. 10, 10.2004, p. 1495-1498.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A novel mutation of GDAP1 associated with Charcot-Marie-Tooth disease in three Italian families
T2 - Evidence for a founder effect
AU - Di Maria, E.
AU - Gulli, R.
AU - Balestra, P.
AU - Cassandrini, D.
AU - Pigullo, S.
AU - Doria-Lamba, L.
AU - Bado, M.
AU - Schenone, A.
AU - Ajmar, F.
AU - Mandich, P.
AU - Bellone, E.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
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U2 - 10.1136/jnnp.2003.028100
DO - 10.1136/jnnp.2003.028100
M3 - Article
VL - 75
SP - 1495
EP - 1498
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
IS - 10
ER -