Abstrakt
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.