Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency

The mutation in a patient with dihydropteridine reductase deficiency has been located and characterized. Polymerase chain reaction (PCR) was used to amplify the coding sequence of human dihydropteridine reductase from the messenger RNA of skin fibroblasts. Chemical cleavage of mismatches indicated a...

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Bibliographic Details
Published inAmerican journal of human genetics Vol. 47; no. 2; pp. 279 - 285
Main Authors HOWELLS, D. W, FORREST, S. M, DAHL, H.-H. M, COTTON, R. G. H
Format Journal Article
LanguageEnglish
Published Chicago, IL University of Chicago Press 01.08.1990
Subjects
Amino Acid Sequence
Aminoacid disorders
Base Sequence
Biological and medical sciences
Codon
Dihydropteridine Reductase - genetics
DNA - genetics
DNA Probes
Errors of metabolism
Humans
insertion
Medical sciences
Metabolic diseases
Molecular Sequence Data
NADH, NADPH Oxidoreductases - deficiency
Nucleic Acid Heteroduplexes - genetics
Phenylketonurias
Polymerase Chain Reaction
RNA, Messenger
Threonine - genetics
Human
Phenylketonuria
Enzyme
Deficiency
Dihydropteridine reductase
Mutation
Genetic disease
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ISSN0002-9297
1537-6605

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Summary:The mutation in a patient with dihydropteridine reductase deficiency has been located and characterized. Polymerase chain reaction (PCR) was used to amplify the coding sequence of human dihydropteridine reductase from the messenger RNA of skin fibroblasts. Chemical cleavage of mismatches indicated a mismatched thymine and cytosine at approximately 117 and 147 bases, respectively, from the end of the probe. Cloning and sequencing of the mutant PCR products revealed the insertion of the triplet ACT (threonine), after alanine 122 (base 390). Amplification of a small region around this mutation by using genomic DNA as the PCR target indicates that the mutation is completely within an exon. Unequal crossing-over at the second base in the preceding alanine codon and duplication of the bases CTA may be the mechanism of mutagenesis. The cleavage site 147 bases from the end of the probe corresponded to the conversion of guanine to adenine at base 420 (CTG to CTA) and does not alter the code for leucine. This change, which was also seen in another dihydropteridine reductase-deficient child and in a control subject probably represents a common neutral polymorphism.
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ISSN:0002-9297
1537-6605