Dataset Information

Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia.

ABSTRACT: We reported elsewhere that an untranslated CTG expansion causes the dominantly inherited neurodegenerative disorder spinocerebellar ataxia type 8 (SCA8). SCA8 shows a complex inheritance pattern with extremes of incomplete penetrance, in which often only one or two affected individuals are found in a given family. SCA8 expansions have also been found in control chromosomes, indicating that separate genetic or environmental factors increase disease penetrance among SCA8-expansion-carrying patients with ataxia. We describe the molecular genetic features and disease penetrance of 37 different families with SCA8 ataxia from the United States, Canada, Japan, and Mexico. Haplotype analysis using 17 STR markers spanning an approximately 1-Mb region was performed on the families with ataxia, on a group of expansion carriers in the general population, and on psychiatric patients, to clarify the genetic basis of the reduced penetrance and to investigate whether CTG expansions among different populations share a common ancestral background. Two major ancestrally related haplotypes (A and A') were found among white families with ataxia, normal controls, and patients with major psychosis, indicating a common ancestral origin of both pathogenic and nonpathogenic SCA8 expansions among whites. Two additional and distinct haplotypes were found among a group of Japanese families with ataxia (haplotype B) and a Mexican family with ataxia (haplotype C). Our finding that SCA8 expansions on three independently arising haplotypes are found among patients with ataxia and cosegregate with ataxia when multiple family members are affected further supports the direct role of the CTG expansion in disease pathogenesis.

SUBMITTER: Ikeda Y

PROVIDER: S-EPMC1182005 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia.

Ikeda Yoshio Y Dalton Joline C JC Moseley Melinda L ML Gardner Kathy L KL Bird Thomas D TD Ashizawa Tetsuo T Seltzer William K WK Pandolfo Massimo M Milunsky Aubrey A Potter Nicholas T NT Shoji Mikio M Vincent John B JB Day John W JW Ranum Laura P W LP

American journal of human genetics 20040519 1

We reported elsewhere that an untranslated CTG expansion causes the dominantly inherited neurodegenerative disorder spinocerebellar ataxia type 8 (SCA8). SCA8 shows a complex inheritance pattern with extremes of incomplete penetrance, in which often only one or two affected individuals are found in a given family. SCA8 expansions have also been found in control chromosomes, indicating that separate genetic or environmental factors increase disease penetrance among SCA8-expansion-carrying patient ...[more]

PMID: 15152344

Similar Datasets

Project description:Spinocerebellar ataxia type 10 (SCA10) is a rare autosomal dominant cerebellar ataxia caused by nucleotide ATTCT expansion in ATXN10 gene. SCA10 has been reported in patients of cerebellar ataxia from Amerindian/Latin America and in East Asian ancestry. A common founder has been ascribed to the origin of ATTCT repeat expansion mutation in both the population. Here we present our investigation of the SCA10 pentanucleotide repeat expansion in 461 SCA patients of the Indian population. The analysis of multi-ethnic at-risk haplotype C-(ATTCT)n-GGC was performed using genotype data of various ethnic population included in the 1000 Genomes Project (KGP) to infer the prevalence of at-risk haplotype in the Indian populations. Unsurprisingly, none of the patient's DNA samples with (ATTCT)n expansion was observed in pathological range, however, the observed normal range of (ATTCT)n was 8-22 repeats, suggesting very rare or absence of the occurrence of SCA10 in Indian SCA patients. The at-risk haplotype, CGGC was found to be the most prevalent haplotype across different populations and no segregation of CGGC haplotype with large normal or small normal ATTCT repeats length was observed. However, on extended haplotype analysis, some lineage of CGGC with a flanking divergence at 5' end was observed specifically in the American or East Asian population but not in other population in KGP dataset. Together, these evidence points towards the absence of SCA10 in Indian population and haplotype-based analysis also suggests its occurrence to be rare in South Asian, European and African population. Further investigations are required to establish the present finding.SignificanceThe implications of the findings of this study are 1.) For the diagnostic work-up of SCAs in the Indian population and to decide upon inclusion of SCA10 in panel based genetic investigations even for Indians living abroad. 2.) The haplotype based inference of its presumptive prevalence through the estimation of at-risk haplotype using population genetics approach (South-Asians as the background) allowed us to estimate the possible absence of SCA10 in Indian population. SCA10 is a rare autosomal dominant cerebellar ataxia mostly reported among SCA patients from Latin America and recently described in East Asia population. The genetic study of SCA10 performed in the unrelated Indian spinocerebellar ataxia patients with heterogeneous ethnicity confirmed its absence from the Indian population and that conforms to population genetic based inference of its rarity or absence. 3.) This approach may be adopted for the screening of other subtypes of SCAs, i.e. other rare SCAs e.g. SCA31, SCA36, and SCA37.

Dataset Information

Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia.

Publications

Spinocerebellar ataxia type 8: molecular genetic comparisons and haplotype analysis of 37 families with ataxia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets