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 122
6G 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-stran
d conformation polymorphism analysis was successfully used to detect m
utation 1226G. This system also revealed the presence of mutation 1297
T in a Jewish patient and a novel point mutation, 1277T, in an Afrikaa
ns-speaking Caucasoid patient. Screening of 360 unrelated, healthy Ash
kenazi Jewish volunteers to estimate the frequency of disease alleles
in the local population led to the detection of 17 carriers: 16 posses
sed the 1226G allele (frequency=0.0222), and one the 1297T allele (fre
quency=0.0014). Using these results, together with the fact that only
92% of ''Gaucher alleles'' would be detected in this study, we estimat
e the disease carrier frequency in the Ashkenazim of South Africa to b
e 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.