1. Phenotypic variability in giant axonal neuropathy
- Author
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Kathrin Huehne, Jean-Michel Vallat, Laurent Magy, S. Assami, D. Grid, Andoni Urtizberea, Tarik Hamadouche, Bernd Rautenstrauss, Meriem Tazir, Sonia Nouioua, Service de Neurologie, Hopital Mustapha, Service de Neurologie [CHU Limoges], CHU Limoges, Biomolécules Thérapies anti-tumorales (EA4021), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Laboratoire de biologie moléculaire, Université M'Hamed Bougara Boumerdes (UMBB), Medical Genetics Center, Friedrich-Baur Institute, and Ludwig-Maximilians-Universität München (LMU)
- Subjects
Male ,Pathology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,DNA Mutational Analysis ,Pyramidal Tracts ,MESH: Pyramidal Tracts ,medicine.disease_cause ,Nerve Fibers, Myelinated ,0302 clinical medicine ,MESH: Child ,Neural Pathways ,Missense mutation ,MESH: Syndrome ,Age of Onset ,MESH: DNA Mutational Analysis ,Child ,Genetics (clinical) ,Giant axonal neuropathy ,Genetics ,0303 health sciences ,Mutation ,Gigaxonin ,MESH: Genetic Predisposition to Disease ,Brain ,Peripheral Nervous System Diseases ,Syndrome ,Phenotype ,Pedigree ,MESH: Nerve Fibers, Myelinated ,MESH: Cerebellar Ataxia ,3. Good health ,medicine.anatomical_structure ,Neurology ,Child, Preschool ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Peripheral Nervous System Diseases ,MESH: Algeria ,Adult ,MESH: Axons ,medicine.medical_specialty ,MESH: Mutation ,Adolescent ,Cerebellar Ataxia ,MESH: Pedigree ,MESH: Age of Onset ,Central nervous system ,Nonsense mutation ,Biology ,MESH: Phenotype ,MESH: Brain ,03 medical and health sciences ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,Humans ,Genetic Predisposition to Disease ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,MESH: Gait Disorders, Neurologic ,Gene ,Gait Disorders, Neurologic ,030304 developmental biology ,MESH: Adolescent ,MESH: Bone Diseases, Developmental ,Bone Diseases, Developmental ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Neural Pathways ,MESH: Child, Preschool ,MESH: Adult ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,medicine.disease ,Axons ,MESH: Male ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Algeria ,Pediatrics, Perinatology and Child Health ,Neurology (clinical) ,MESH: Female ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery - Abstract
International audience; 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.
- Published
- 2009
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