Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies): genetic analysis of three unrelated SCA2 families.
Autosomal dominant cerebellar ataxias (ADCAs) are a group of neurodegenerative disorders that are clinically and genetically heterogeneous. We report here a genetic linkage study, with five chromosome 12q markers, of three Martinican families with ADCA type 1, for which the spinocerebellar ataxia 1 (SCA1) locus was excluded. Linkage to the SCA2 locus was demonstrated with a maximal lead score of 6.64 at theta = 0.00 with marker D12S354. Recombinational events observed by haplotype reconstruction demonstrated that the SCA2 locus is located in an approximately 7-cM interval flanked by D12S105 and D12S79. Using the z(max)-1 method, multipoint analysis further reduced the candidate interval for SCA2 to a region of 5 cM. Two families shared a common haplotype at loci spanning 7 cM, which suggests a founder effect, whereas a different haplotype segregated with the disease in the third family. Finally, a mean anticipation of 12+/-14 years was found in parent-child couples, with no parental sex effect, suggesting that the disease might be caused by an expanded and unstable triplet repeat.
Lezin
A
A
Laboratoire de Biologie Moléculaire, CTS-Höpital Perre Zobda-Quitman,Fort-de-France, Martinique.
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G
G
Stevanin
G
G
Smadja
D
D
Vernant
J C
JC
Dürr
A
A
Martial
J
J
Buisson
G G
GG
Bellance
R
R
Chneiweiss
H
H
Agid
Y
Y
Brice
A
A
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D005190:Family; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D008395:Martinique; D008875:Middle Aged; D010375:Pedigree; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000235:genetics*
D005819:Genetic Markers