Specific founding events can be found for the most common European mutations (Eisensmith et al, 1992), and it seems that PAH mutations have many origins and have spread in several populations. (Stuhrmann et al, 1989)
One of the enzyme defects that cause phenylketonuria is present in approximately one in every ten thousand (1/10000) births in Northern Europeans (Guthrie and Susi, 1963)
The carrier frequency in the general UK population is about 1/50 ie one person out of fifty carries one mutated copy of the PAH gene.
There is a great deal of variety in incidence between countries and race. Hofman et al. (1991) quote an incidence of 1/4500 in Ireland, 1/16000 in Switzerland, 1/50000 in US Blacks and 1/15,000 in US Caucasians. Phenylketonuria is rare in Ashkenazi Jews Cohen et al. 1961
There are many different mutations, this must be taken into account in carrier detection and prenatal screening programs. Dianzini et al. (1990) shows that the most common in Northern Europe are the splicing mutation IVS12DS, G-A, +1 and the missense mutation ARG408 to TRP.
Great genetic diversity has been found in the UK and it was shown that there was a distribution of the more common mutations that showed differences between North and South (Tyfield et al, 1997).
Woolf (1986) suggested that the PKU mutation might have given heterozygotes an evolutionary advantage. He thought that an increased resistance to toxins produced by moulds growing on grain and foodstuffs might lead to an advantage in times when food supplies were low and mouldy food had to be eaten. The idea of a heterozygote advantage, supports the finding that PAH mutations have multiple origins and with this advantage would spread through populations.
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