A mutation in CYP11B1 (Arg-448 → His) associated with steroid 11β-hydroxylase deficiency in Jews of Moroccan origin

Perrin C. White, Jakob Dupont, Maria I. New, Esther Leiberman, Zeev Hochberg, Ariel Rösler

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

Steroid 11β-hydroxylase (P450c11) deficiency (failure to convert 11-deoxycortisol to cortisol) causes less than 10% of cases of congenital adrenal hyperplasia in most populations, but it is relatively frequent in Jews of Moroccan origin. P450c11 is encoded by the CYP11B1 gene which is located on chromosome 8q22 along with a homologous gene of unknown function, CYP11B2. To identify mutations in CYP11B1 associated with 11β-hydroxylase deficiency in Moroccan Jews, oligonucleotides were used that selectively amplified portions of CYP11B1 in polymerase chain reactions without amplifying CYP11B2. Sequence analysis of amplified fragments from one patient revealed a single base substitution in exon 8, codon 448 from CGC (arginine) to CAC (histidine). This residue is within the ''heme binding'' peptide that contains a cysteine that is a ligand to the heme group. The equivalent of Arg-448 is found in every known eukaryotic P450, and therefore it seems likely that a mutation of this residue would adversely affect enzymatic activity. 11 of 12 affected alleles from six Moroccan Jewish families carried the mutation in codon 448. This mutation is not normally present in CYP11B2 and thus appears to have arisen in CYP11B1 as a true point mutation rather than a gene conversion.

Original languageEnglish (US)
Pages (from-to)1664-1667
Number of pages4
JournalJournal of Clinical Investigation
Volume87
Issue number5
DOIs
StatePublished - Jan 1 1991

Keywords

  • Autosomal recessive disorder
  • Congenital adrenal hyperplasia
  • Cytochrome P450
  • Hypertension
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Medicine(all)

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