Hg. Eiken et al., RELATIVE FREQUENCY, HETEROGENEITY AND GEOGRAPHIC CLUSTERING OF PKU MUTATIONS IN NORWAY, European journal of human genetics, 4(4), 1996, pp. 205-213
We have analysed 236 Norwegian phenylketonuria (PKU) alleles by a comb
ination of mutation scanning methods, restriction enzyme-based assays
and DNA sequencing. Thirty-three different mutations constituted 99.6%
of all mutant alleles (only 1 allele remains unidentified), 23 of the
se have been identified also in other European countries. Twenty were
predicted missense mutations, 6 splice mutations, 4 nonsense mutations
and 2 deletion mutations and 1 mutation disrupted the start codon. Th
e 8 most common mutations represented 83.5% of the PKU alleles, with s
ingle allele frequencies ranging from 5.9 to 15.7%. Four of these muta
tions (R261Q, R408W, Y414C, and IVS12nt1) are commonly occurring also
in PKU patients in other European countries, while the other 4 (G46S,
G272X, F299C, and R408Q) have higher frequencies in Norway than in any
other country studied. Six mutations (I65T, L249F, P281L, Y356X, R158
Q, and R252W) have frequencies between 0.8% and 2.1%, and 19 mutations
were encountered only once. The majority of PKU mutations were found
on the same RFLP/VNTR haplotype backgrounds in Norway as in other Euro
pean populations, suggesting that only a few of the mutations may repr
esent recurrent mutations (<3.4%). Among 10 mutations only reported fo
r our population, we detected 2 de novo mutations (0.8%) arisen in Nor
way. From the birthplaces of the probands' grandparents, each mutation
seemed to have an individual geographic distribution within Norway, w
ith patterns of local mutation clustering. Our observations are compat
ible with multiple founder effects and genetic drift for the distribut
ion of PKU mutations within Norway.