Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency

Janice E. Finkelstein, Clair Ann Francomano, Saul W. Brusilow, Monica D. Traystman

Research output: Contribution to journalArticle

Abstract

Ornithine transcarbamylase (ornithine carbamoyl-transferase, EC 2.1.3.3) deficiency is an X-linked inborn error of metabolism with considerable phenotypic variability in affected males. Using a combination of the polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE), we defined a mutation in a family in whom affected males have significant residual enzyme activity. A C → T change in the first nucleotide of codon 277 resulted in the substitution of a tryptophan for an arginine at amino acid 245 of the mature protein. This change appears to represent a deleterious mutation rather than a polymorphism on the basis of several factors: the change occurs at a highly conserved arginine residue, significant size and change differences exist between arginine and tryptophan, and this change was not seen on DGGE screening of 26 unrelated individuals representing 43 chromosomes. Diagnosis of an at-risk male newborn in this family was performed using direct mutational analysis. In families with partial enzyme deficiencies in whom biochemical data may be difficult to evaluate, direct detection of mutations at the OTC locus permits definitive diagnosis. This represents the first description of a mutation in late onset OTC deficiency and demonstrates direct mutational analysis by DGGE for prospective diagnosis in a genetic disorder.

Original languageEnglish (US)
Pages (from-to)167-172
Number of pages6
JournalGenomics
Volume7
Issue number2
DOIs
StatePublished - 1990

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Ornithine Carbamoyltransferase Deficiency Disease
Denaturing Gradient Gel Electrophoresis
Delayed Diagnosis
Arginine
Mutation
Tryptophan
Carboxyl and Carbamoyl Transferases
Ornithine Carbamoyltransferase
Inborn Errors Metabolism
Inborn Genetic Diseases
Ornithine
Enzymes
Codon
Nucleotides
Chromosomes
Amino Acids
Polymerase Chain Reaction
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Use of denaturing gradient gel electrophoresis for detection of mutation and prospective diagnosis in late onset ornithine transcarbamylase deficiency. / Finkelstein, Janice E.; Francomano, Clair Ann; Brusilow, Saul W.; Traystman, Monica D.

In: Genomics, Vol. 7, No. 2, 1990, p. 167-172.

Research output: Contribution to journalArticle

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