Prevalence of myotonic dystrophy in Israeli Jewish communities: Inter‐community variation and founder premutations

Abstract

In a comprehensive epidemiological survey among Jews living in Israel, the average prevalence of myotonic dystrophy (DM) was 15.7/10(5) (1 case in 6369) with intercommunity variations; the Ashkenazi Jews had the lowest rate, 5.7/10(5) (1 case in 17544) as compared to the rate in the Sephardim/Oriental Jews 20/10(5) (1 case in 5000) and the in the Yemenite Jews 47.3/10(5) (1 case in 2114). The rate of unrelated DM-sibships per 10(6) people of each community was used as an estimate of the transition rate from stable to unstable DMPK-(CTG)(n) alleles assuming that each transition is a beginning of a new DM sibship. This study indicated that the difference in the incidence of DM is a result of higher mutation rate in the non-Ashkenazi Jews (>50/10(6)) as compared to the rate in the Ashkenazi Jews (16.3/10(6)). The intragenic haplotype of the DM alleles was the same as that of the DM in many populations all over the world. However, two DM closely linked markers D19S207 and D19S112 were in linkage disequilibrium with the DM mutation in patients of Yemenite and Moroccan (the largest subgroup in the Sephardim Jews) extractions and not in the Ashkenazi patients. This observation indicated a common ancestral origin for the DM premutation in patients of the same ethnic origin. We concluded that the difference in the prevalence of DM among the Jewish communities is a consequence of founder premutations in the non-Ashkenazi Jewish communities.

Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland

“…13 In Jewish communities, an average prevalence of 15.7 per 100 000 was reported in a study including 416 DM1 patients of which 307 were diagnosed genetically and 109 were clinically diagnosed. 14 The same study reported even higher prevalences in two Jewish subgroups: 20.0 per 100 000 in Sephardim/Oriental Jews and 47.3 per 100 000 in Yemenite Jews. Among Jews, Ashkenazi had the lowest prevalence with 5.7 per 100 000.…”

“…10 As the advent of molecular genetic testing for DM1, several prevalence studies have been reported, [11][12][13][14][15]17 but so far no large-scale population studies have been performed. Most of the reported studies were based on the number of diagnosed patients related to the corresponding total population in a certain region.…”

Anatomy of a founder effect: myotonic dystrophy in Northeastern Quebec

“…Interestingly, two major haplotypes (in addition to their derivatives) were observed in French-Canadians from Northeastern Quebec and from the Outaouais region, which were distinct from the major haplotype characteristic of Canadian DM1 patients of non-French descent. An example of the diversification of a founder effect in an isolated population is provided by Segel et al (2003), who studied the prevalence of DM1 in three Israeli-Jewish populations: the Ashkenazim, Sepharadim and Yemenites. They found that DM1 prevalence varied widely, ranging from as low as 1/17,544 in the Ashkenazim to 1/5,000 in the Sepharadim and up to 1/2,114 in the Yemenites.…”

A Nationwide, Population-Based Prevalence Study of Genetic Muscle Disorders

“…The observed ethnic difference in the prevalence of myotonic dystrophy means that for Māori, and Pasifika, myotonic dystrophy was less common than facioscapulohumeral and the dystrophinopathies, a finding not previously described. Lower prevalence of myotonic dystrophy has been found in other ethnic minority groups in South Africa [12] and Israel [13]. However, these previous studies did not compare prevalence of myotonic dystrophy to other genetic muscle disorders.…”