GDAP1 mutations in Czech families with early-onset CMT

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Neuromuscular Disorders Vol. 17 Issue 6 Pages 482-489 (June 2007)

GDAP1 mutations in Czech families with early-onset CMT

L. Baránkováa, E. Vyhnálkováb, S. Züchnerc, R. Mazaneca, I.

Sakmaryováb, P. Vondráèekd, L. Merlinie, M. Bojara, E. Nelisf, P. De

Jonghef, P. Seemanb

Abstract:

Mutations in the ganglioside-induced differentiation associated

protein-1 gene (GDAP1) cause autosomal recessive (AR) demyelinating

or axonal Charcot-Marie-Tooth neuropathy (CMT). In order to

establish the spectrum and frequency of GDAP1 mutations in Czech

population, we sequenced GDAP1 in 74 Czech patients from 69

unrelated families with early-onset demyelinating or axonal CMT

compatible with AR inheritance. We identified three isolated

patients with GDAP1 mutations in both alleles. In one additional

sporadic and one familial case, the second pathogenic mutation

remained unknown.

Overall, we detected two different mutations, a novel R191X nonsense

and a L239F missense mutation. L239F previously described in a

German–Italian family is a prevalent mutation in Czech population

and we give evidence for its common ancestral origin. All Czech

GDAP1 patients developed involvement of all four limbs evident by

the end of second decade, except for one isolated patient showing

very slow disease progression. All patients displayed axonal type of

neuropathy.

Keywords: HMSN type II, Charcot-Marie-Tooth disease, Autosomal

recessive CMT2, GDAP1, R191X, L239F

a Department of Neurology, 2nd School of Medicine,

University Prague, Prague, Czech Republic

b Department of Child Neurology, 2nd School of Medicine,

University Prague, Prague, Czech Republic

c Center for Human Genetics, Duke University Medical Center, Durham,

NC, USA

d Department of Child Neurology, Masaryk University Brno, Brno,

Czech Republic

e Department of Experimental & Diagnostic Medicine, University of

Ferrara, Ferrara, Italy

f Molecular Genetics Department, Flanders Interuniversity Institute

for Biotechnology, University of Antwerp, Antwerp, Belgium