title: A narcolepsy susceptibility locus maps to a 5 Mb region of chromosome 21q.
abstract: The genetic basis of human narcolepsy remains poorly understood. Multiplex families with full-blown narcolepsy-cataplexy are rare, whereas families with both narcolepsy-cataplexy and excessive daytime sleepiness without cataplexy are more common. We performed a genomewide linkage analysis in a large French family with four members affected with narcolepsy-cataplexy and 10 others with isolated recurrent naps or lapses into sleep. Only three regions showed logarithm of odds (LOD) scores greater than 1 in two-point linkage analysis (D6S1960, D11S2359, and D21S228). Genotyping additional markers provided support for linkage to 9 markers on chromosome 21 (maximum two-point LOD score, 3.36 at D21S1245). The multipoint linkage analysis using SimWalk2 provided further evidence for linkage to the same region (maximum parametric LOD score, 4.00 at 21GT26K). A single haplotype was shared by all affected individuals and informative crossovers indicated that the elusive gene that confers susceptibility to narcolepsy is likely to be located between markers D21S267 and ABCG1, in a 5.15 Mb region of 21q.
authors.affiliation: Service de Neurologie B, Hôpital Gui-de-Chauliac, Montpellier, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Dauvilliers
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Neidhart
authors.forename: Bertrand
authors.initials: B
authors.lastname: Carlander
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Michel
authors.initials: M
authors.lastname: Billiard
authors.forename: Mehdi
authors.initials: M
authors.lastname: Tafti
mesh_terms: D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D009290:Narcolepsy / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping / Q000379:methods
chemical_list: D005819:Genetic Markers