HETEROGENEOUS ETHNIC DISTRIBUTION OF THE 844INS68 IN THE CYSTATHIONINE BETA-SYNTHASE GENE

A novel mutation in the cystathisnine beta-synthase (CBS) gene (a 68-b p insertion in the coding region of exon 8: 844ins68) was recently des cribed, but its prevalence in different human populations is unknown. We analyzed the prevalence of the 68-bp insertion in the CBS gene in 4 05 unrelated individuals (8 10 chromosomes) of European, African, Asia n and Amerindian origins, PCR amplification of a DNA fragment containi ng exon 8 of the CBS gene was employed, In addition, screening for the T833C CBS mutation by BsrI digestion was carried out in all samples b earing the 844ins68 mutation, since both mutations were previously rep orted to be associated in cis, The insertion was found in heterozygosi ty in 14 out of 104 whites (13.5%), was absent among Asians, and was f ound solely in 1 out of 220 Amerindian chromosomes analyzed, whereas a much higher prevalence was observed among blacks (37.7% of heterozygo tes and 4% of mutant homozygotes), Furthermore, the T833C CBS mutation was found to cosegregate in cis with 844ins68 in all carriers of the insertion. The finding of the double mutant among blacks and Caucasian s suggests that it antedated the racial divergence between Africans an d non-Africans, and provides evidence for a partly or completely neutr alizing effect conferred by the 68-bp insertion, since it allows the s kipping of the T833C mutation, Our study represents the first analysis of the 844ins68 insertion in the CBS gene in different human populati ons, and reveals an extensive ethnic and geographic variability associ ated with this mutation.