BIOMAT Database Logo BIOMAT Database Logo

Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations. 1998

I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Dipartimento di Scienze Pediatriche e dell' Adolescenza, Università degli Studi di Torino, Italy. dianzani@pediatria.unito.it

Dihydropteridine reductase (DHPR) is an enzyme involved in recycling of tetrahydrobiopterin (BH4), the cofactor of the aromatic amino acid hydroxylases. Its deficiency is characterized by hyperphenylalaninemia due to the secondary defect of phenylalanine hydroxylase and depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases. The DHPR cDNA has been cloned and mapped on 4p15.3. In the present study we report the genomic structure of the DHPR gene (QDPR). This gene includes seven exons within a range of 84-564 bp; the corresponding introns are flanked by canonic splice junctions. We also present a panel of PCR primers complementary to intronic sequences that greatly facilitates amplification of the gene and provides a genomic DNA approach for mutation detection. We have used this approach to study six patients with DHPR deficiency. Four known mutations (G23D, H158Y, IVS5G+ 1A, R221X) and two new mutations (Y150C and G218ins9bp) were found. The Y150C mutation was found in compound heterozygosity with G23D, a mutation always associated with a severe phenotype in homozygous patients. This patient has an intermediate phenotype (good response to monotherapy with BH4). The mutant enzyme for Y150C was expressed in an E. coli system. Comparison of its kinetic parameters with those of the G23D mutant enzyme showed that it is not as effective as the wild-type enzyme, but is more active than the G23D mutant. This patient's intermediate phenotype is thus due to the mild DHPR mutation Y150C. Correlations between genotypes and phenotypes were also found for the other mutations.

UI MeSH Term Description Entries
D007438 Introns Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes. Intervening Sequences,Sequences, Intervening,Intervening Sequence,Intron,Sequence, Intervening
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D010661 Phenylketonurias A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme PHENYLALANINE HYDROXYLASE or less frequently by reduced activity of DIHYDROPTERIDINE REDUCTASE (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; SEIZURES; skin HYPOPIGMENTATION; ECZEMA; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952). Biopterin Deficiency,Dihydropteridine Reductase Deficiency Disease,Hyperphenylalaninemia, Non-Phenylketonuric,Phenylalanine Hydroxylase Deficiency Disease,BH4 Deficiency,DHPR Deficiency,Deficiency Disease, Dihydropteridine Reductase,Deficiency Disease, Phenylalanine Hydroxylase,Deficiency Disease, Phenylalanine Hydroxylase, Severe,Dihydropteridine Reductase Deficiency,Folling Disease,Folling's Disease,HPABH4C,Hyperphenylalaninaemia,Hyperphenylalaninemia Caused by a Defect in Biopterin Metabolism,Hyperphenylalaninemia, BH4-Deficient, C,Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To DHPR Deficiency,Non-Phenylketonuric Hyperphenylalaninemia,Oligophrenia Phenylpyruvica,PAH Deficiency,PKU, Atypical,Phenylalanine Hydroxylase Deficiency,Phenylalanine Hydroxylase Deficiency Disease, Severe,Phenylketonuria,Phenylketonuria I,Phenylketonuria II,Phenylketonuria Type 2,Phenylketonuria, Atypical,Phenylketonuria, Classical,QDPR Deficiency,Quinoid Dihydropteridine Reductase Deficiency,Tetrahydrobiopterin Deficiency,Atypical PKU,Atypical Phenylketonuria,Biopterin Deficiencies,Classical Phenylketonuria,Deficiency, BH4,Deficiency, Biopterin,Deficiency, DHPR,Deficiency, Dihydropteridine Reductase,Deficiency, PAH,Deficiency, Phenylalanine Hydroxylase,Deficiency, QDPR,Deficiency, Tetrahydrobiopterin,Disease, Folling,Disease, Folling's,Hyperphenylalaninemia, Non Phenylketonuric,Non Phenylketonuric Hyperphenylalaninemia,Non-Phenylketonuric Hyperphenylalaninemias
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D004093 Dihydropteridine Reductase An enzyme that catalyzes the reduction of 6,7-dihydropteridine to 5,6,7,8-tetrahydropteridine in the presence of NADP+. Defects in the enzyme are a cause of PHENYLKETONURIA II. Formerly listed as EC 1.6.99.7. 6,7-Dihydropteridine Reductase,6,7 Dihydropteridine Reductase,Reductase, 6,7-Dihydropteridine,Reductase, Dihydropteridine
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D005091 Exons The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA. Mini-Exon,Exon,Mini Exon,Mini-Exons
D005796 Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic

Related Publications

I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Two mutations of dihydropteridine reductase deficiency.
February 1988, Archives of disease in childhood,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency.
June 1993, Journal of medical genetics,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency.
May 1995, American journal of human genetics,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency.
August 2014, World journal of pediatrics : WJP,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Physical and genetic localization of quinonoid dihydropteridine reductase gene (QDPR) on short arm of chromosome 4.
September 1987, Somatic cell and molecular genetics,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Identification and in vitro expression of mutations causing dihydropteridine reductase deficiency.
June 1993, Biochemistry,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Molecular analysis of dihydropteridine reductase deficiency: identification of two novel mutations in Japanese patients.
October 1997, Human genetics,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Amelogenesis imperfecta phenotype-genotype correlations with two amelogenin gene mutations.
April 2002, Archives of oral biology,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
Mutations in CYP11B1 gene: phenotype-genotype correlations.
October 2003, American journal of medical genetics. Part A,
I Dianzani, and L de Sanctis, and P M Smooker, and T J Gough, and C Alliaudi, and A Brusco, and M Spada, and N Blau, and M Dobos, and H P Zhang, and N Yang, and A Ponzone, and W L Armarego, and R G Cotton
The spectrum of mutations in dihydropteridine reductase deficiency.
January 1993, Advances in experimental medicine and biology,
Copied contents to your clipboard!