R339H and P453S

CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions

Arno Helmberg, Maria Teresa Tusie-Luna, Marco Tabarelli, Reinhard Kofler, Perrin C. White

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia, an inherited disorder of cortisol biosynthesis. All mutations thus far characterized that cause this disorder appear to result from recombinations between the gene encoding the enzyme, CYP21B (CYP21), and the adjacent pseudogene, CYP21A (CYP21P). These are either deletions caused by unequal crossing-over during meiosis or apparent transfers of deleterious sequences from CYP21A to CYP21B, a phenomenon termed gene conversion. However, a small percentage of alleles do not carry such a mutation. We analyzed DNA from a patient with the mild, nonclassic form of 21-hydroxylase deficiency, who carried one allele that had no gene conversions detectable by hybridization with oligonucleotide probes. Sequence analysis revealed that this allele carried two missense mutations, R339H and P453S, neither of which has been previously observed in CYP21A or CYP21B. Each of these mutations was introduced into CYP21 cDNA which was then expressed in COS1 cells using a vaccinia virus system. Each mutation reduced the ability of the enzyme to 21-hydroxylate 17-hydroxy-progesterone to 50% of normal and the ability to metabolize progesterone to 20% of normal. Thus, each of these mutations represents a potential nonclassic 21-hydroxylase deficiency allele that is not the result of an apparent gene conversion.

Original languageEnglish (US)
Pages (from-to)1318-1322
Number of pages5
JournalMolecular Endocrinology
Volume6
Issue number8
StatePublished - Aug 1992

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Steroid 21-Hydroxylase
Gene Conversion
Mutation
Alleles
Progesterone
Congenital Adrenal Hyperplasia
Pseudogenes
Oligonucleotide Probes
Vaccinia virus
Meiosis
Missense Mutation
Enzymes
Genetic Recombination
Sequence Analysis
Hydrocortisone
Complementary DNA
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
DNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

R339H and P453S : CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions. / Helmberg, Arno; Tusie-Luna, Maria Teresa; Tabarelli, Marco; Kofler, Reinhard; White, Perrin C.

In: Molecular Endocrinology, Vol. 6, No. 8, 08.1992, p. 1318-1322.

Research output: Contribution to journalArticle

Helmberg, Arno ; Tusie-Luna, Maria Teresa ; Tabarelli, Marco ; Kofler, Reinhard ; White, Perrin C. / R339H and P453S : CYP21 mutations associated with nonclassic steroid 21-hydroxylase deficiency that are not apparent gene conversions. In: Molecular Endocrinology. 1992 ; Vol. 6, No. 8. pp. 1318-1322.
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