GDAP1 mutations in Czech families with early-onset CMT

[Guest guest]

Neuromuscul Disord. 2007 Apr 10

GDAP1 mutations in Czech families with early-onset CMT.

Barankova L, Vyhnalkova E, Zuchner S, Mazanec R, Sakmaryova I,

Vondracek P, Merlini L, Bojar M, Nelis E, De Jonghe P, Seeman P.

Department of Neurology, 2nd School of Medicine, University

Prague, Prague, Czech Republic.

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.