title: Homozygosity mapping of giant axonal neuropathy gene to chromosome 16q24.1.
abstract: Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder described as a symmetrical distal neuropathy, with peripheral axons dilated by accumulation of 10 nm neurofilaments (NF) and a severe course of the disease. The observation of kinky or curly hairs is not a constant finding. The GAN1 locus was localized by homozygosity mapping to chromosome 16 q24.1 in a 3 (4) cM interval flanked by the markers D16S3073 and D16S505 (D16S511) in three non-related Tunisian families, showing a genetic homogeneity in these families. Two point lod-score calculation between the linked haplotype and the disease locus was 14.2 at theta(max) = 0. The patients share a slow course of the disease. The differences in the course of the disease between Tunisian and non-Tunisian patients suggest a possible genetic heterogeneity, which is why the present linkage has been referred to as GAN1. The biochemical defect in GAN1 should help to understand the mechanisms involved in NF accumulations as in other neurological diseases (ALS, SMA).
authors.affiliation: Laboratoire de Neuropathologie et Neurobiologie Moléculaire, Institut National de Neurologie, La Rabta, Tunis, Tunisia.
authors.forename: C
authors.initials: C
authors.lastname: Ben Hamida
authors.forename: L
authors.initials: L
authors.lastname: Cavalier
authors.forename: S
authors.initials: S
authors.lastname: Belal
authors.forename: H
authors.initials: H
authors.lastname: Sanhaji
authors.forename: N
authors.initials: N
authors.lastname: Nadal
authors.forename: C
authors.initials: C
authors.lastname: Barhoumi
authors.forename: N
authors.initials: N
authors.lastname: M'Rissa
authors.forename: N
authors.initials: N
authors.lastname: Marzouki
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamida
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: F
authors.initials: F
authors.lastname: Hentati
mesh_terms: D001369:Axons / Q000473:pathology*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree