Distal hereditary motor neuropathy (HMN) is a clinically and genetically heterogeneous group of disorders affecting spinal alpha-motor neurons. Since 2001, mutations in six different genes have been identified for autosomal dominant distal HMN; glycyl-tRNA synthetase (GARS), dynactin 1 (DCTN1), small heat shock 27 kDa protein 1 (HSPB1), small heat shock 22 kDa protein 8 (HSPB8), Berardinelli-Seip congenital lipodystrophy (BSCL2) and senataxin (SETX). In addition a mutation in the (VAMP)-associated protein B and C (VAPB) was found in several Brazilian families with complex and atypical forms of autosomal dominantly inherited motor neuron disease. We have investigated the distribution of mutations in these seven genes in a cohort of 112 familial and isolated patients with a diagnosis of distal motor neuropathy and found nine different disease-causing mutations in HSPB8, HSPB1, BSCL2 and SETX in 17 patients of whom 10 have been previously reported. No mutations were found in GARS, DCTN1 and VAPB. The phenotypic features of patients with mutations in HSPB8, HSPB1, BSCL2 and SETX fit within the distal HMN classification, with only one exception; a C-terminal HSPB1-mutation was associated with upper motor neuron signs. Furthermore, we provide evidence for a genetic mosaicism in transmitting an HSPB1 mutation. This study, performed in a large cohort of familial and isolated distal HMN patients, clearly confirms the genetic and phenotypic heterogeneity of distal HMN and provides a basis for the development of algorithms for diagnostic mutation screening in this group of disorders.

• MeSH
• elektrofyziologie MeSH
• fenotyp MeSH
• genotyp MeSH
• haplotypy MeSH
• hereditární motorické a senzitivní neuropatie * genetika   patofyziologie   MeSH
• lidé MeSH
• lidské chromozomy, pár 11 genetika   MeSH
• missense mutace * MeSH
• mozaicismus MeSH
• nádorové proteiny genetika   MeSH
• protein-serin-threoninkinasy genetika   MeSH
• proteiny tepelného šoku HSP27 MeSH
• proteiny tepelného šoku genetika   MeSH
• proteiny vázající GTP - gama-podjednotky genetika   MeSH
• RNA-helikasy genetika   MeSH
• rodokmen MeSH
• sekvence nukleotidů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH