Autosomal dominant cerebellar ataxia type I in Martinique (French West Indies): Genetic analysis of three unrelated SCA2 families |
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Authors: | Agnès Lezin Jenny Martial Géraldine Cancel Giovanni Stevanin Alexander Dürr Yves Agid Alexis Brice Didier Smadja Jean-Claude Vernant Georges-Gabriel Buisson Rémy Bellance Hervé Chneiweiss |
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Institution: | (1) Laboratoire de Biologie Moléculaire, CTS-Hôpital Perre Zobda-Quitman, Fort-de-France, Martinique;(2) INSERM U289, Hôpital de la Salpêtrière, 47, Boulevard del'Hôpital, Paris, France;(3) Service de Neurologie, Hôpital Pierre Zobda-Quitman, Fort-de-France, Martinique;(4) INSERM U114, Collège de France, Paris, France |
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Abstract: | 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 I, for which the spinocerebellar ataxia 1 (SCA1) locus was excluded. Linkage to the SCA2 locus was demonstrated with a maximal lod score of 6.64 at = 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 D 12S 105 and D12S79. Using thez
max-l 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. |
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