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| Teresa Matamá |
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Rua Campo Alegre, 823, 4150-180 Porto, Portugal
e-mail: matama@ibmc.up.pt |
Poster Presentation: |
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| PORTUGUESE FAMILIES WITH DENTATORUBROPALLIDOLUYSIAN ATROPHY (DRPLA) SHARE A COMMON HAPLOTYPE OF ASIAN ORIGIN. |
| Matamá1, S. Martins1, L. Guimarăes1,2, J. Sequeiros1,2 and I. Silveira1 | |
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1UnIGENe, IBMC, and 2Laboratório de Genética Médica, ICBAS, Universidade do Porto, Portugal |
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| Dentatorubropallidoluysian atrophy (DRPLA) is an autosomal dominant spinocerebellar ataxia characterized by variable combinations of gait ataxia, myoclonic epilepsy and dementia. This neurodegenerative disorder is caused by a (CAG)n expansion in exon 5 of the DRPLA gene, located on the short arm of chromosome 12. DRPLA is most prevalent in Japan but several families of non-Japanese ancestry have been identified. Expanded DRPLA alleles of Asian and Caucasian ancestry share a common haplotype that is also associated with longer repeats found in the normal Asian population. The prevalence of dominant spinocerebellar ataxias is associated to the frequency of large normal alleles, which may contribute to the generation of the expanded alleles. DRPLA is very rare in Western countries though five Portuguese families have been identified so far. Interestingly, no association between the frequency of DRPLA and the frequency of large normal alleles has been found in the Portuguese population. To gain insight into the origin of expanded DRPLA alleles in Portuguese families, two previously reported intragenic biallelic polymorphisms in intron 1 (A1010G, system A) and intron 3 (T1865C, system B) were analysed by PCR-SSCP and sequencing. Only 3 of the 4 possible haplotypes were found - A1-B2, A2-B2, A1-B1. The expanded alleles segregated exclusively with the A1-B1 haplotype, as have been shown in Asian families. These results support the hypothesis of DRPLA expansions have evolved from an ancient haplotype of Asian origin.
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