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ERIC Number: EJ793219
Record Type: Journal
Publication Date: 2008-May
Pages: 11
Abstractor: Author
Reference Count: N/A
ISBN: N/A
ISSN: ISSN-0006-8950
Relative Contribution of Mutations in Genes for Autosomal Dominant Distal Hereditary Motor Neuropathies: A Genotype-Phenotype Correlation Study
Dierick, Ines; Baets, Jonathan; Irobi, Joy; Jacobs, An; De Vriendt, Els; Deconinck, Tine; Merlini, Luciano; Van den Bergh, Peter; Rasic, Vedrana Milic; Robberecht, Wim; Fischer, Dirk; Morales, Raul Juntas; Mitrovic, Zoran; Seeman, Pavel; Mazanec, Radim; Kochanski, Andrzej; Jordanova, Albena; Auer-Grumbach, Michaela; Helderman-van den Enden, A. T. J. M.; Wokke, John H. J.; Nelis, Eva; De Jonghe, Peter; Timmerman, Vincent
Brain, v131 n5 p1217-1227 May 2008
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.
Oxford University Press. Great Clarendon Street, Oxford, OX2 6DP, UK. Tel: +44-1865-353907; Fax: +44-1865-353485; e-mail: jnls.cust.serv@oxfordjournals.org; Web site: http://brain.oxfordjournals.org/
Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A
Identifiers - Location: Brazil