COMPLETE SPECTRUM OF PAH MUTATIONS IN TATARIA - PRESENCE OF SLAVIC, TURKIC AND SCANDINAVIAN MUTATIONS

Phenylketonuria (PKU) is an autosomal recessive disorder associated wi th a deficiency of hepatic phenylalanine hydroxylase (PAH). Although t he molecular lesions present in the PAH genes of PKU patients have pre viously been determined in several Slavic populations, little is known regarding the molecular basis of PKU in the non-Slavic populations of the former Soviet Union. Guthrie card samples from twenty-one classic al PKU patients residing in the Tatarian Republic were examined by a c ombination of denaturing gradient gel electrophoresis and direct seque nce analysis. Twelve patients were of Tatarian ancestry, five were of Russian ancestry, and four were of mixed Tatarian and Russian ancestry . Two of the Tatarian patients were related, sharing one mutant allele . The single major allele identified in this study was R408W/RFLP hapl otype 2/VNTR 3, which was present on 11/14 or 78.6% of all mutant chro mosomes of Slavic origin, but on only 10/27 or 37.0% of mutant chromos omes of Tatarian origin. This result suggests that this allele was int roduced into central Asian populations during the eastward expansion o f Slavs across the Eurasian landmass. A significant influence of Turki c peoples on Tatars can be inferred from the presence of R261Q, IVS10n t546g-->a, L48S, IVS2nt5g-->c and P281L, all of which are relatively c ommon among Turks or have been observed in Mediterranean populations. Together, these alleles are present on 11/27 or 40.7% of all mutant ch romosomes in ethnic Tatars. Surprisingly, the common Scandinavian muta tion IVS12nt1g-->a was also present in Tataria, as was the Delta agE22 1D222fs mutation found previously only in Denmark. Thus, some direct o r indirect gene flow from Scandinavian into Tataria seems evident. Fin ally, the complete absence of PAH mutations previously observed in Ori ental populations suggests that there was little gene flow into Tatari a from Eastern Asia.