title: Phenotypic variability in giant axonal neuropathy.
abstract: Giant axonal neuropathy (GAN), a severe childhood disorder affecting both the peripheral nerves and the central nervous system, is due to mutations in the GAN gene encoding gigaxonin, a protein implicated in the cytoskeletal functions and dynamics. In the majority of the GAN series reported to date, patients had the classical clinical phenotype characterized by a severe axonal neuropathy with kinky hair and early onset CNS involvement including cerebellar and pyramidal signs. We present 12 patients (6 families) with GAN mutations and different clinical phenotypes. Four families were harbouring an identical homozygous nonsense mutation but with different severe clinical phenotypes, one patient had a novel missense homozygous mutation with a peculiar moderate phenotype and prominent skeletal deformations. The last family (4 patients) harbouring a homozygous missense mutation had the mildest form of the disease. In contrast with recent reported series of patients with typical GAN clinical features, the present series demonstrate obvious clinical heterogeneity.
authors.affiliation: Laboratoire de Recherche de Neurosciences, Université d'Alger, Service de Neurologie, Centre Hospitalier Universitaire Mustapha, 1 place du 1er Mai, Algiers 16000, Algeria. meriemtazir@yahoo.com
authors.forename: Meriem
authors.initials: M
authors.lastname: Tazir
authors.forename: Sonia
authors.initials: S
authors.lastname: Nouioua
authors.forename: Laurent
authors.initials: L
authors.lastname: Magy
authors.forename: Kathrin
authors.initials: K
authors.lastname: Huehne
authors.forename: Salima
authors.initials: S
authors.lastname: Assami
authors.forename: Andoni
authors.initials: A
authors.lastname: Urtizberea
authors.forename: Djamel
authors.initials: D
authors.lastname: Grid
authors.forename: Tarik
authors.initials: T
authors.lastname: Hamadouche
authors.forename: Bernd
authors.initials: B
authors.lastname: Rautenstrauss
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vallat
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000462:Algeria; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002524:Cerebellar Ataxia / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology; D013577:Syndrome