Absence of spinocerebellar ataxia type 3/Machado–Joseph disease within ataxic patients in the Czech population

Abstract

Although spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease is the most common type of SCA worldwide, we did not identify any cases of the disease amongst SCA patients in the Czech population. It has been proposed that the prevalence of large normal alleles correlates with the frequency of various types of SCA. We have therefore attempted to resolve the absence of SCA3 in our population by investigating, within 204 normal chromosomes, the frequency and nature of CAG repeats as well as two intragenic polymorphisms. We found that large normal alleles with more than 33 CAG repeats were observed at a frequency of only 0.49%. Whereas most of the expanded alleles worldwide have the CA haplotype, this was the least common (5.4%) variant observed in our study, although it was associated with a larger mean CAG repeat length (26.9). We postulate that the absence of SCA3 in the Czech population might be explained by the lack of large normal alleles and consequently a relatively small reservoir for aberrant CAG expansions at the SCA3 locus.

High frequency of Machado-Joseph disease identified in Southeastern Chinese kindreds with spinocerebellar ataxia

“…4A). The difference in the frequency of large ANs between the present study and other studies involving Japanese [9], Indian [10], Czech [11] populations and a combined population comprised of Acadian, Black, Caucasian, Inuit and Thai [21] is shown in table 1.…”

“…The most common allele contained 14 CAG repeats, which was also the most common allele found in the studies of Limprasert et al [21] and Takano et al [9]. The frequency of large ANs (>27 repeats) was 0.28, which is higher than the frequency in previously studied populations [9-11,21]. …”

Cambodian founder effect for spinocerebellar ataxia type 3 (Machado–Joseph disease)

“…SCA 3 is the most common type overall with a frequency of about 21%. Outside of Asia the frequency of families with SCA 3 varies from a high of more than 60% in Portugal and Brazil to a low of less than 5% in South Africa and no cases found in a Czech population [7,8]. SCA 3 represents about 20% of autosomal dominant ataxias in the United States.…”

Spinocerebellar ataxias: microsatellite and allele frequency in unaffected and affected individuals

“…According to this study we found alleles with a size equal to or greater than 27 (CAG)n in the MJD gene, and MJD is the most frequent ataxia among patients. These findings have an epidemiological interest as these alleles appear to be in haplotypes that have a great potential for expansion by gene conversion 19,[36][37][38][39][40] .…”

“…Fluorescent labels were selected based on the normal allele size ranges described above for each locus, while taking care to ensure that loci with overlapping size ranges were given different labels. The following reactions were carried out: one triplex reaction with 1.5 pmol of each primer for SCA1 (36), SCA2 (10) and SCA6 (18); a single reaction with 12pmol of each SCA3 primer (SCA3F 5'NED-CTGGCCTTTCACATGG 3' and SCA3R 5' CCA-GTCACTACTTTGATTCGTG 3') and a reaction with 15 pmol of each SCA7 primer (SCA7F 5'VIC-TTGTAGGAGCGGAAAGAAT-GTC 3'and SCA7R 5' CTTCAGGACTGGGCAGAGG 3'). The last two pairs of primers (SCA3 pair and SCA7 pair) were designed for the present study.…”