title: Possible genetic heterogeneity of spinocerebellar ataxia linked to chromosome 15.
abstract: Autosomal dominant spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative disorders. We investigated an SCA family from Serbia of Roma ethnic origin; four affected and nine unaffected family members underwent a detailed neurological examination. The presenting symptom in all patients was gait unsteadiness in early adulthood. Additional features included pyramidal signs, depression, and cognitive impairment. The condition follows an autosomal dominant pattern of inheritance. After excluding repeat expansions in nine known SCA genes, a genome-wide linkage analysis with 412 microsatellite markers localized the putative disease gene to a 40.7 cM (42.5 Mb) region on chromosome 15q between markers D15S1006 and D15S116. The maximum model-based multipoint LOD score was 1.75. This region is only 4.3 Mb away from the SCA11 (TTBK2) gene. Accordingly, mutations in TTBK2 were not found, suggesting a second SCA gene on chromosome 15q as cause of this novel form of SCA. In addition, we excluded alterations in two candidate genes in the linked region, namely expansion of a polyglutamine-coding CAG repeat in ARID3B and mutations in SEMA6D.
authors.affiliation: Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Luübeck, Luübeck, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Weissbach
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Natasa
authors.initials: N
authors.lastname: Dragasević
authors.forename: Christine
authors.initials: C
authors.lastname: Zühlke
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Raković
authors.forename: Miodrag
authors.initials: M
authors.lastname: Guzvić
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Butz
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Igor
authors.initials: I
authors.lastname: Petrović
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
mesh_terms: D000328:Adult; D000368:Aged; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D055771:Serbia / Q000453:epidemiology / Q000208:ethnology; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: C120893:ARID3B protein, human; D004268:DNA-Binding Proteins