Possible genetic heterogeneity of spinocerebellar ataxia linked to chromosome 15.
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.
Weissbach
Anne
A
Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Luübeck, Luübeck, Germany.
Djarmati
Ana
A
Klein
Christine
C
Dragasević
Natasa
N
Zühlke
Christine
C
Raković
Aleksandar
A
Guzvić
Miodrag
M
Butz
Elisabeth
E
Tönnies
Holger
H
Siebert
Reiner
R
Petrović
Igor
I
Svetel
Marina
M
Kostić
Vladimir S
VS
Lohmann
Katja
K
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
C120893:ARID3B protein, human; D004268:DNA-Binding Proteins