The molecular characterization of Gaucher disease in South Africa

DNA from 29 southern African Gaucher disease patients was analyzed for five common Gaucher disease mutations: 1226G, 1448C, 84GG, IVS2 + 1 and 1504T. The origins of the patients were as follows: 14 Ashkenazi Jews; 6 Gentile Caucasoids; 8 Negroids; and one of mixed ancestry. The 1226G allele accounted for 80% of disease alleles in the Jewish patients, 50% of alleles in the Gentile Caucasoid patients and was absent from the Negroid patients. The 1448C allele was present in both the Jewish (1 of 24 alleles) and Negroid patients (3 of 16 alleles). Single-strand conformation polymorphism analysis was successfully used to detect mutation 1226G. This system also revealed the presence of mutation 1297T in a Jewish patient and a novel point mutation, 1277T, in an Afrikaans-speaking Caucasoid patient. Screening of 360 unrelated, healthy Ashkenazi Jewish volunteers to estimate the frequency of disease alleles in the local population led to the detection of 17 carriers: 16 possessed the 1226G allele (frequency = 0.0222), and one the 1297T allele (frequency = 0.0014). Using these results, together with the fact that only 92% of "Gaucher alleles" would be detected in this study, we estimate the disease carrier frequency in the Ashkenazim of South Africa to be 0.05, or approximately 1:20. A reliable carrier screening programme can now be offered to the local Jewish community. The majority of the disease alleles in the two Gentile groups remain uncharacterized.