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

187 Citations (Scopus)

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
StatePublished - May 1991

Fingerprint

Steroid 11-beta-Hydroxylase
Jews
Cytochrome P-450 CYP11B2
Mutation
Heme
Codon
Cortodoxone
Congenital Adrenal Hyperplasia
Gene Conversion
Mixed Function Oxygenases
Point Mutation
Histidine
Oligonucleotides
Genes
Cysteine
Sequence Analysis
Arginine
Hydrocortisone
Exons
Chromosomes

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A mutation in CYP11B1 (Arg-448 → His) associated with steroid 11β-hydroxylase deficiency in jews of Moroccan origin. / White, Perrin C.; Dupont, Jakob; New, Maria I.; Leiberman, Esther; Hochberg, Zeev; Rösler, Ariel.

In: Journal of Clinical Investigation, Vol. 87, No. 5, 05.1991, p. 1664-1667.

Research output: Contribution to journalArticle

White, Perrin C. ; Dupont, Jakob ; New, Maria I. ; Leiberman, Esther ; Hochberg, Zeev ; Rösler, Ariel. / A mutation in CYP11B1 (Arg-448 → His) associated with steroid 11β-hydroxylase deficiency in jews of Moroccan origin. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 5. pp. 1664-1667.
@article{5881b83024af45bebd3e0cd236dece59,
title = "A mutation in CYP11B1 (Arg-448 → His) associated with steroid 11β-hydroxylase deficiency in jews of Moroccan origin",
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.",
keywords = "Autosomal recessive disorder, Congenital adrenal hyperplasia, Cytochrome P450, Hypertension, Polymerase chain reaction",
author = "White, {Perrin C.} and Jakob Dupont and New, {Maria I.} and Esther Leiberman and Zeev Hochberg and Ariel R{\"o}sler",
year = "1991",
month = "5",
language = "English (US)",
volume = "87",
pages = "1664--1667",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - A mutation in CYP11B1 (Arg-448 → His) associated with steroid 11β-hydroxylase deficiency in jews of Moroccan origin

AU - White, Perrin C.

AU - Dupont, Jakob

AU - New, Maria I.

AU - Leiberman, Esther

AU - Hochberg, Zeev

AU - Rösler, Ariel

PY - 1991/5

Y1 - 1991/5

N2 - 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.

AB - 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.

KW - Autosomal recessive disorder

KW - Congenital adrenal hyperplasia

KW - Cytochrome P450

KW - Hypertension

KW - Polymerase chain reaction

UR - http://www.scopus.com/inward/record.url?scp=0025847381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025847381&partnerID=8YFLogxK

M3 - Article

VL - 87

SP - 1664

EP - 1667

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -