Prevalence of myotonic dystrophy in Israeli Jewish communities: inter-community variation and founder premutations

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.