title: Low proportion of whole exon deletions causing phenylketonuria in Denmark and Germany.
abstract: Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by mutations of the gene encoding phenylalanine hydroxylase (PAH). More than 500 different PAH mutations have been identified and about 90% of these are single base mutations. Although the identification rate of the PAH mutations is generally very high, some variants remain unidentified. A fraction of these mutations are the result of genomic deletions or duplications, which are not recognized with standard PCR-based methods. Here we present the results of exon deletion or duplication analysis in a total of 34 families, in which two mutations had not been identified using conventional diagnostic screening techniques. Using multiplex ligation-dependent probe amplification (MLPA), we found a deletion covering exon 1 and exon 2 (c.1-?_168+?del) in one patient, a deletion of exon 3 (c.169-?_352+?del) in four patients, and a deletion of exon 5 (c.442-?_509+?del) in two patients. A deletion was thus detected in about 20% (7/34) of the families tested. Out of a combined cohort of 570 independent PKU patients from Denmark and Germany, exon deletions were identified in a total of four patients. The estimated allelic frequency of exon deletions in PKU patients in these two populations is therefore below 0.5%.
authors.affiliation: Kennedy Institute-National Eye Clinic, Glostrup, Denmark. lbm@kennedy.dk
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Birk Møller
authors.forename: Anders O H
authors.initials: AO
authors.lastname: Nygren
authors.forename: Patrick
authors.initials: P
authors.lastname: Scott
authors.forename: Pia
authors.initials: P
authors.lastname: Hougaard
authors.forename: Jytte
authors.initials: J
authors.lastname: Bieber Nielsen
authors.forename: Caroline
authors.initials: C
authors.lastname: Hartmann
authors.forename: Flemming
authors.initials: F
authors.lastname: Güttler
authors.forename: Linda
authors.initials: L
authors.lastname: Tyfield
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003718:Denmark; D005091:Exons; D005787:Gene Frequency; D005820:Genetic Testing; D005858:Germany; D006801:Humans; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: D010651:Phenylalanine Hydroxylase