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Low proportion of whole exon deletions causing phenylketonuria in Denmark and Germany
Author(s) -
Birk Møller Lisbeth,
Nygren Anders O.H.,
Scott Patrick,
Hougaard Pia,
Bieber Nielsen Jytte,
Hartmann Caroline,
Güttler Flemming,
Tyfield Linda,
Zschocke Johannes
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9481
Subject(s) - multiplex ligation dependent probe amplification , exon , biology , genetics , gene duplication , mutation , allele , phenylalanine hydroxylase , microbiology and biotechnology , multiplex , frameshift mutation , gene , phenylalanine , amino acid
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%. © 2007 Wiley‐Liss, Inc.