MUTATION PROFILES OF PHENYLKETONURIA IN QUEBEC POPULATIONS - EVIDENCEOF STRATIFICATION AND NOVEL MUTATIONS

Independent phenylketonuria (PKU) chromosomes (n=109) representing 80% of a proband cohort in Quebec province carry 18 different identified mutations in 20 different mutation/haplotype combinations. The study r eported here, the third in a series on Quebec populations, was done in the Montreal region and predominantly on French Canadians. It has ide ntified three novel mutations (A309D, D338Y, and 1054/1055delG [352fs] ) and one unusual mutation/RFLP haplotype combination (E280K on Hp 2). The relative frequencies and distribution of PKU mutations were then compared in three regions and population subsets (eastern Quebec, Fren ch Canadian; western Quebec, French Canadian; and Montreal, non-French Canadian). The distributions of the prevalent and rare mutations are nonrandom and provide evidence for genetic stratification. The latter and the presence of eight unusual mutation/haplotype combinations in Q uebec families with European ancestries (the aforementioned four and M 1V, I65T, S349P, and R408W on Hp 1) corroborate demographic and anthro pologic evidence, from elsewhere, for different origins of French Cana dians in eastern and western Quebec.