Phenylketonuria mutations in Germany

We report the spectrum of mutations and associated modified haplotypes in p atients with phenylketonuria living in Germany. A total of 546 independent alleles was investigated, including 411 of German and 65 of Turkish descent . Mutations were identified for 535 PKU alleles (98%) and there were 91 dif ferent mutations. The most common mutation was R408W on 22% of alleles. Two mutations, IVS12+1G-->A and IVS10-11G-->A accounted for just under 10% of alleles, whereas the remaining mutations were found al:relative frequencies of 6% or less; 43 mutations were observed once only. IVS10-11G-->A was the most common mutation (38% of alleles) in the subgroup of patients of Turki sh descent. Modified haplotypes were determined from the analysis of four s ilent mutations, three diallelic restriction fragment length polymorphisms, a variable number of tandem repeats minisatellite and a short tandem repea t microsatellite in the phenylalanine hydroxylase gene, showing that a cons iderable proportion of mutations must have recurred in independent founders ; other mutations may have changed chromosomal haplo-type backgrounds by ge ne conversion. The spectrum of PKU mutations in Germany reflects the histor y of a heterogenous Central European population living at the crossroads of migration throughout the centuries.