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Low proportion of whole exon deletions causing phenylketonuria in Denmark and Germany.

https://arctichealth.org/en/permalink/ahliterature165648
Source
Hum Mutat. 2007 Feb;28(2):207
Publication Type
Article
Date
Feb-2007
Author
Lisbeth Birk Møller
Anders O H Nygren
Patrick Scott
Pia Hougaard
Jytte Bieber Nielsen
Caroline Hartmann
Flemming Güttler
Linda Tyfield
Johannes Zschocke
Author Affiliation
Kennedy Institute-National Eye Clinic, Glostrup, Denmark. lbm@kennedy.dk
Source
Hum Mutat. 2007 Feb;28(2):207
Date
Feb-2007
Language
English
Publication Type
Article
Keywords
Cohort Studies
DNA Mutational Analysis
Denmark
Exons
Gene Frequency
Genetic Testing
Germany
Humans
Phenylalanine Hydroxylase - genetics
Phenylketonurias - diagnosis - genetics
Polymerase Chain Reaction
Sequence Deletion
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%.
PubMed ID
17221866 View in PubMed
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Mutational and phenotypical spectrum of phenylalanine hydroxylase deficiency in Denmark.

https://arctichealth.org/en/permalink/ahliterature283899
Source
Clin Genet. 2016 Sep;90(3):247-51
Publication Type
Article
Date
Sep-2016
Author
A. Bayat
S. Yasmeen
A. Lund
JB Nielsen
LB Møller
Source
Clin Genet. 2016 Sep;90(3):247-51
Date
Sep-2016
Language
English
Publication Type
Article
Keywords
Alleles
Denmark
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Mutation
Phenotype
Phenylalanine Hydroxylase - genetics
Phenylketonurias - diagnosis - genetics - pathology
Abstract
We describe the genotypes of the complete cohort, from 1967 to 2014, of phenylketonuria (PKU) patients in Denmark, in total 376 patients. A total of 752 independent alleles were investigated. Mutations were identified on 744 PKU alleles (98.9%). In total, 82 different mutations were present in the cohort. The most frequent mutation c.1315+1G>A (IVS12+1G>A) was found on 25.80% of the 744 alleles. Other very frequent mutations were c.1222C>T (p.R408W) (16.93%) and c.1241A>G (p.Y414C) (11.15%). Among the identified mutations, five mutations; c.532G>A (p.E178K), c.730C>T (p.P244S), c.925G>A (p.A309T), c.1228T>A (p.F410I), and c.1199+4A>G (IVS11+4A>G) have not been reported previously. The metabolic phenotypes of PKU are classified into four categories; 'classical PKU', 'moderate PKU', 'mild PKU' and 'mild hyperphenylalaninemia'. In this study, we assigned the phenotypic outcome of three of the five novel mutations and furthermore six not previously classified mutations to one of the four PKU categories.
PubMed ID
26542770 View in PubMed
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[Phenylketonuria. Report of third diagnosed case in Finland].

https://arctichealth.org/en/permalink/ahliterature112125
Source
Duodecim. 1966;82(20):983-6
Publication Type
Article
Date
1966

Polymorphic DNA haplotypes at the phenylalanine hydroxylase locus and their relation to phenotype in Swedish phenylketonuria families.

https://arctichealth.org/en/permalink/ahliterature37169
Source
Hum Genet. 1991 May;87(1):11-7
Publication Type
Article
Date
May-1991
Author
E. Svensson
U. von Döbeln
L. Hagenfeldt
Author Affiliation
Department of Clinical Chemistry, Huddinge University Hospital, Sweden.
Source
Hum Genet. 1991 May;87(1):11-7
Date
May-1991
Language
English
Publication Type
Article
Keywords
Alleles
DNA - genetics
Haplotypes
Heterozygote
Humans
Infant, Newborn
Mutation
Phenotype
Phenylalanine Hydroxylase - genetics
Phenylketonurias - diagnosis - genetics
Polymorphism, Restriction Fragment Length
Prenatal Diagnosis
Research Support, Non-U.S. Gov't
Sweden
Abstract
The genetic heterogeneity at the phenylalanine hydroxylase (PAH) locus was studied in 88 families including 93 of the 105 children with phenylketonuria (PKU) or hyperphenylalaninemia (HPA) detected through the Swedish neonatal screening program from 1966 to the end of 1986. Haplotypes based on eight restriction fragment length polymorphisms (RFLPs) at the PAH locus could be constructed for 132 normal and 136 mutant alleles. The normal alleles were of 27 different RFLP haplotypes, 9 of which have not been described previously, but there was a dominance of a few haplotypes common to many European populations. The distribution of mutant alleles was significantly different from that in neighboring countries, even though over 90% of all mutant alleles were confined to six RFLP haplotypes, also prevalent in other European populations. Allele-specific oligonucleotide hybridization analysis for the Arg408 to Trp408 mutation and for the G to A splicing mutation in intron 12 showed exceptions to the previously reported linkage of these mutations to mutant haplotypes 2 and 3, respectively. Correlation of mutant alleles with clinical phenotypes pointed to the presence of at least two different mutations associated with each of six haplotypes. We argue that PKU/HPA in the Swedish population may be caused by at least 13 different mutations in addition to the 4 already identified. The theoretical informativity of RFLP analysis in heterozygote detection and prenatal diagnosis in PKU/HPA families was estimated at approximately 85%. Carrier detection could, in effect, be accomplished for 88% of the 56 healthy siblings in the families studied.
PubMed ID
1674714 View in PubMed
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