ACMG January 2009

Diseases commonly grouped together as “Jewish Genetic Disorders” (JGDs) range in incidence from 1/900 to 1/40,000 in the Jewish community, specifically those individuals of Ashkenazi (eastern European) heritage. Although some of these disorders in isolation would be considered rare, the overall carrier rate in this population is significant, with between 1 in 4 and 1 in 5 Ashkenazi Jews carrying a mutation for any one of these disorders. Because of genetic drift in combination with historical and social factors, certain autosomal recessive disorders have been found to occur at a higher incidence (e.g., TaySachs disease) or almost exclusively in this population (e.g., familial dysautonomia) whereas other disorders may be as common as in other high risk groups (e.g., cystic fibrosis). However, the commonality for JGDs is that all exhibit the founder mutation phenomenon whereby only 1–3 mutations account for the vast majority of deleterious alterations found in this specific population.