Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy.

Authors :: Nelis E
Erdem S
Van Den Bergh PY
Belpaire-Dethiou MC
Ceuterick C
Van Gerwen V
Cuesta A
Pedrola L
Palau F
Gabreëls-Festen AA
Verellen C
Tan E
Demirci M
Van Broeckhoven C
De Jonghe P
Topaloglu H
Timmerman V
Source :: Neurology [Neurology] 2002 Dec 24; Vol. 59 (12), pp. 1865-72.
Publication Year :: 2002
Abstract: Background: Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis.<br />Methods: The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1.<br />Results: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C).<br />Conclusions: Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.