caa a22 4500 46798509X CHVBK 20180323112529.0 cr unu---uuuuu 170328e19900801xx s 000 0 eng 10.1007/BF00206750 doi (NATIONALLICENCE)springer-10.1007/BF00206750 Two mutations within the coding sequence of the phenylalanine hydroxylase gene [Elektronische Daten] [Elisabeth Svensson, Björn Andersson, Lars Hagenfeldt] Summary: Two previously unidentified mutations at the phenylalanine hydroxylase locus were found during a study of the relationship between genotype and phenotype in phenylketonuria and hyperphenylalaninemia. One mutation eliminates the BamHI site in exon 7 and the other eliminates the HindIII site in exon 11 of the phenylalanine hydroxylase gene. They were suspected because of deviating restriction fragment patterns and confirmed by amplification, via the polymerase chain reaction, of exon 7 and exon 11, respectively, followed by digestion with the appropriate restriction enzyme. Direct sequencing of amplified mutant exon 7 revealed a G/C to T/A transversion at the first base of codon 272, substituting a GGA glycine codon for a UGA stop codon. Direct sequencing of amplified mutant exon 11 revealed a deletion of codon 364, a CTT leucine codon. The exon 7 mutation can be expected to result in a truncated protein and the exon 11 mutation in the elimination of an amino acid in the catalytic region of the enzyme. A patient who is a compound heterozygote for these two mutations has classical phenylketonuria. It is concluded that each of the two mutations leads to a profound loss of enzymatic activity. The segregation of these mutations with disease alleles in 4 and 2 families, respectively, supports the hypothesis that multiple mutations at the phenylalanine hydroxylase locus explain the variable phenylalanine tolerance in patients with phenylalanine hydroxylase deficiency. Springer-Verlag, 1990 Svensson Elisabeth Department of Clinical Chemistry, Karolinska Hospital, S-10401, Stockholm, Sweden aut Andersson Björn Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut Hagenfeldt Lars Department of Clinical Chemistry, Karolinska Hospital, S-10401, Stockholm, Sweden aut Human Genetics Springer-Verlag 85/3(1990-08-01), 300-304 0340-6717 85:3<300 1990 85 439 https://doi.org/10.1007/BF00206750 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00206750 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Svensson Elisabeth Department of Clinical Chemistry, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 700 1- Andersson Björn Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 700 1- Hagenfeldt Lars Department of Clinical Chemistry, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 85/3(1990-08-01), 300-304 0340-6717 85:3<300 1990 85 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer