title: Evaluation of a fetus at risk for dihydropteridine reductase deficiency by direct mutation analysis using denaturing gradient gel electrophoresis.
abstract: Dihydropteridine reductase (DHPR) is an enzyme involved in the recycling of tetrahydrobiopterin (BH(4)), which is an obligate co-factor of the aromatic amino acid hydroxylases. DHPR deficiency is a rare, autosomal recessive disorder caused by mutations in the QDPR gene. DHPR-deficient patients are diagnosed by a lack of response to a low phenylalanine diet and by severe neurological symptoms. Final diagnosis is made by measurements of neurotransmitters and pterin metabolites in cerebrospinal fluid (CSF) and urine, in addition to DHPR enzyme activity, which can be assessed in whole red blood cells. Treatment of DHPR deficiency can be difficult and the outcome is not always satisfying, even if all treatment strategies are followed. Therefore prenatal diagnosis is of great importance in affected families. Prenatal diagnosis is possible by measuring DHPR activity in different cell types but this is time consuming. More than 25 different mutations have to date been identified in the QDPR gene and direct identification of a mutation in a fetus would be easy and rapid. We have developed a method based on denaturing gradient gel electrophoresis (DGGE) for the analysis of the QDPR gene. The method is useful for rapid and simultaneous scanning of all exons and flanking intronic sequences of the QDPR gene. We describe the first prenatal diagnosis conducted using this method.
authors.affiliation: Hacettepe University, Department of Pediatrics, Division of Nutrition and Metabolism, TR-06100 Ankara, Turkey. serap@gen.hun.edu.tr
authors.forename: H S
authors.initials: HS
authors.lastname: Kalkanoglu
authors.forename: A
authors.initials: A
authors.lastname: Romstad
authors.forename: T
authors.initials: T
authors.lastname: Coşkun
authors.forename: F
authors.initials: F
authors.lastname: Güttler
mesh_terms: D000483:Alleles; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis / Q000379:methods*; D004093:Dihydropteridine Reductase / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D010375:Pedigree; D010661:Phenylketonurias; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011489:Protein Denaturation
chemical_list: D004093:Dihydropteridine Reductase