Phenylketonuria mutations in Germany.
We report the spectrum of mutations and associated modified haplotypes in patients 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 different 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 at 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 Turkish descent. Modified haplotypes were determined from the analysis of four silent mutations, three diallelic restriction fragment length polymorphisms, a variable number of tandem repeats minisatellite and a short tandem repeat microsatellite in the phenylalanine hydroxylase gene, showing that a considerable proportion of mutations must have recurred in independent founders; other mutations may have changed chromosomal haplotype backgrounds by gene conversion. The spectrum of PKU mutations in Germany reflects the history of a heterogenous Central European population living at the crossroads of migration throughout the centuries.
Department of Neuropaediatrics and Metabolic Diseases, University Children's Hospital, Philipps University, Marburg, Germany. zschocke@mailer.uni-marburg.de
J
J
Zschocke
G F
GF
Hoffmann
D005091:Exons; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D007438:Introns; D018598:Minisatellite Repeats; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion; D014421:Turkey
D010651:Phenylalanine Hydroxylase