title: Giant axonal neuropathy locus refinement to a < 590 kb critical interval.
abstract: Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder, characterised clinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, skeletal abnormalities and, ultrastructurally, by axons in the central and peripheral nervous systems distended by masses of tightly woven neurofilaments. We recently localised the GAN locus in 16q24.1 to a 5-cM interval between the D16S507 and D16S511 markers by homozygosity mapping in three consanguineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite markers. Using these markers, we have refined the position of our previous flanking recombinants. We also identified a shared haplotype between two Tunisian families and a small region of homozygosity in a Turkish family with distant consanguinity, both suggesting the occurrence of historic recombinations and supporting the conclusions based on the phase-known recombinations. Taken together, these results allow us to establish a transcription map of the region, and to narrow down the GAN position to a < 590 kb critical interval, an important step toward the identification of the defective gene.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, CU de Strasbourg, France.
authors.forename: L
authors.initials: L
authors.lastname: Cavalier
authors.forename: C
authors.initials: C
authors.lastname: BenHamida
authors.forename: R
authors.initials: R
authors.lastname: Amouri
authors.forename: S
authors.initials: S
authors.lastname: Belal
authors.forename: P
authors.initials: P
authors.lastname: Bomont
authors.forename: N
authors.initials: N
authors.lastname: Lagarde
authors.forename: L
authors.initials: L
authors.lastname: Gressin
authors.forename: D
authors.initials: D
authors.lastname: Callen
authors.forename: E
authors.initials: E
authors.lastname: Demir
authors.forename: H
authors.initials: H
authors.lastname: Topaloglu
authors.forename: P
authors.initials: P
authors.lastname: Landrieu
authors.forename: C
authors.initials: C
authors.lastname: Ioos
authors.forename: M B
authors.initials: MB
authors.lastname: 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*; D001842:Bone and Bones / Q000002:abnormalities*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003241:Consanguinity; D020451:Contig Mapping; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000473:pathology; D018895:Microsatellite Repeats; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011115:Polyneuropathies / Q000235:genetics / Q000473:pathology
chemical_list: D017931:DNA Primers