PHENYLKETONURIA MUTATIONS AND LINKED HAPLOTYPES IN THE LITHUANIAN POPULATION - ORIGIN OF THE MOST COMMON R408W MUTATION

A genealogical study was performed in Lithuanian phenylketonuria (PKU) families with the aim of tracing the origins of the R408W/haplotype 2 /VNTR3 allele, The relative frequency of six phenylalanine hydroxylase (PAH) mutations (R408W, R158Q, R261Q, Q272X, IVS10nt-11g-->a, and IVS 12nt1g-->a) common in Eastern European populations and their associati on with variable number of tandem repeat (VNTR) and short tandem repea t (STR) sites in the PAH gene were examined in 130 PKU Lithuanian chro mosomes, including 95 of Baltic, 28 of Slavonic and 7 of unknown origi n. R408W was found to be the most frequent (70%) mutation in both Bait s or Slavonians with a uniform frequency distribution, No statisticall y significant differences in the frequency distribution of the other m utations analysed were found, In Baits and Slavonians, the R408W mutat ion is strongly associated with the three-copy VNTR and the 240-bp STR allele, The frequency of this association is 68% in both ethnic group s. The genealogical data provided in this paper indicate that the most common R408W/VNTR3/STR240 allele arose in ancient times possibly amon g pre-Indo-Europeans and suggest that the high frequency of the R408W mutation and associated minihaplotype in Baits of Lithuania is due to a founder effect.