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Identification of seven novel mutations in the GAN gene
Author(s) -
Bomont P.,
Ioos C.,
Yalcinkaya C.,
Korinthenberg R.,
Vallat JM.,
Assami S.,
Munnich A.,
Chabrol B.,
Kurlemann G.,
Tazir M.,
Koenig M.
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9122
Subject(s) - biology , missense mutation , nonsense mutation , neurofilament , genetics , gene , mutation , intermediate filament , nonsense , loss function , microbiology and biotechnology , cell , phenotype , cytoskeleton , immunohistochemistry , immunology
Abstract Giant axonal neuropathy (GAN) is a severe early onset neurodegenerative disorder affecting both the peripheral nerves and the central nervous system. The diagnosis is based on the presence of characteristic giant axons on nerve biopsy. In GAN, the integrity of the intermediate filament network is altered. Indeed, abnormal accumulation of the intermediate filaments has been reported in different cell types, including in the swollen axons, which are filled with neurofilaments. We identified the defective protein, gigaxonin, of unknown function, and reported fourteen distinct mutations in twelve families of various origins. Two additional mutations have been recently reported. In the present study, we analysed the GAN gene in 6 families, and identified seven novel mutations: three nonsense and two missense mutations and two deletions. In addition, the molecular result for an already reported family was re‐evaluated. In this family, the R269Q “polymorphism” is in fact the pathogenic mutation. © 2003 Wiley‐Liss, Inc.