New mutations, genotype phenotype studies and manifesting carriers in giant axonal neuropathy

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 78; no. 11; pp. 1267 - 1270
• Main Authors: Houlden, Henry, Groves, Mike, Miedzybrodzka, Zosia, Roper, Helen, Willis, Tracey, Winer, John, Cole, Gaynor, Reilly, Mary M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.11.2007; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adolescent; Adult; Age; Axons - pathology; Biological and medical sciences; Biomedical research; Biopsy; Brain - pathology; Child; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 16; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Cytoskeletal Proteins - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Families & family life; Female; Funding; Genes; Genes, Recessive - genetics; Genetic Carrier Screening; Genotype; Genotype & phenotype; Homozygote; Hospitals; Humans; Male; Medical research; Medical sciences; Microscopy, Electron; Multiple sclerosis; Mutation; Nerve Fibers, Myelinated - pathology; Nervous system (semeiology, syndromes); Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; Neurologic Examination; Neurology; Neuromuscular diseases; Patients; Phenotype; Short Report; Studies; Sural Nerve - pathology; Giant axonal neuropathy; Genotype; Phenotype; Nervous system diseases; Mutation; Carrier
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.2007.118968

Giant axonal neuropathy (GAN; MIM 256850) is a severe childhood onset autosomal recessive sensorimotor neuropathy affecting both the peripheral nerves and the central nervous system. Bomont and colleagues identified a novel ubiquitously expressed gene they named Gigaxonin on chromosome 16q24 as the cause of GAN in a number of families. We analysed five families with GAN for mutations in the Gigaxonin gene and mutations were found in four families; three families had homozygous mutations, one had two compound heterozygous mutations and one family had no mutation identified. All families had the typical clinical features, kinky hair and nerve biopsy. We report some unusual clinical features associated with GAN and Gigaxonin mutations as well as confirm the heterogeneity in GAN and the identification of two families with manifesting carriers.