Large-scale molecular screening for galactosemia alleles in a pan-ethnic population

Abstract.

DNA samples from 4,796 subjects from diverse ethnic groups were screened for five frequently encountered galactose-1-phosphate uridyl transferase (GALT) mutations: S135L (cDNA nt 404C→T, as numbered from the initiator ATG codon, with A=1); Q188R (cDNA nt 563A→G); K285 N (cDNA nt 855G→T); the Duarte variant, N314D (cDNA nt 940A→G); and the Los Angeles variant, which contains L218L (cDNA nt 652C→T) and N314D. Among Whites, the gene frequency of the Q188R mutation was 0.29%, and that of the K285 N mutation was 0.062%. Only one S135L mutation was encountered among 505 African-Americans (gene frequency 0.10%). The pan-ethnic gene frequencies of the Duarte and the Los Angeles variants were 5.1% and 2.7%, respectively. Both of these frequencies were significantly less among African-Americans and Asians than among Whites and Hispanics. Native Americans revealed a higher incidence of the both variants. Based upon the gene frequency of the Q188R mutation in the White population, the birth incidence of classic galactosemia is estimated at one patient per 47,000 in the White population. This prevalence would be increased by inbreeding. It agrees well with the results from newborn screening programs and is only minimally higher than that reported in most studies, suggesting that most, if not all, infants with the galactosemia genotype are born and survive sufficiently long to be screened.