A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement.

Iceland was settled during the late 9th and early 10th centuries AD by Vikings who arrived from Norway and the British Isles. Although it is generally acknowledged that the Vikings brought with them Celtic slaves, the relative contribution of these peoples to the modern Icelandic gene pool has been a matter of considerable discussion. Most population genetic studies using classical markers have indicated a large Irish genetic contribution. We have investigated the molecular basis of phenylketonuria (PKU) in 17 Icelandic patients and found 9 different mutations in the phenylalanine hydroxylase gene. One novel mutation, Y377fsdelT, accounts for more than 40% of the mutant chromosomes. Haplotype data support a common ancestral origin of the mutation, and genealogical examination extending back more than 5 generations shows that this mutation has probably arisen in an isolated part of southern Iceland and was enriched by a founder effect. At least 7 PKU mutations have originated outside iceland. The almost exclusively Scandinavian background of these mutations and the complete absence of common Irish PKU mutations strongly support historical and linguistic evidence of a predominant Scandinavian heritage of the Icelandic people.