Premium
Mutational and phenotypical spectrum of phenylalanine hydroxylase deficiency in Denmark
Author(s) -
Bayat A.,
Yasmeen S.,
Lund A.,
Nielsen J.B.,
Møller L.B.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12692
Subject(s) - hyperphenylalaninemia , phenylalanine hydroxylase , genetics , allele , phenotype , mutation , compound heterozygosity , cohort , genotype , medicine , biology , phenylalanine , gene , amino acid
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.