title: Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families.
abstract: Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393. Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. lviollet@afm.genethon.fr
authors.forename: Louis
authors.initials: L
authors.lastname: Viollet
authors.forename: Mohammed
authors.initials: M
authors.lastname: Zarhrate
authors.forename: Isabelle
authors.initials: I
authors.lastname: Maystadt
authors.forename: Brigitte
authors.initials: B
authors.lastname: Estournet-Mathiaut
authors.forename: Annie
authors.initials: A
authors.lastname: Barois
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Michèle
authors.initials: M
authors.lastname: Mayer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Bruno
authors.initials: B
authors.lastname: LeHeup
authors.forename: Veronica
authors.initials: V
authors.lastname: Cusin
authors.forename: Thierry
authors.initials: T
authors.lastname: Billette De Villemeur
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Anne
authors.initials: A
authors.lastname: Touzery-De Villepin
authors.forename: Anne
authors.initials: A
authors.lastname: Delaubier
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Kaplan
authors.forename: Marc
authors.initials: M
authors.lastname: Jeanpierre
authors.forename: Joshué
authors.initials: J
authors.lastname: Feingold
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002908:Chronic Disease; D005060:Europe; D005190:Family; D005260:Female; D018703:Founder Effect; D005808:Genes, Recessive; D005819:Genetic Markers; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010375:Pedigree; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers