CoChat
Sign Up
Cited by 183Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

A Mutation (Pro-30 to Leu) in CYP 21 Represents a Potential Nonclassic Steroid 21-Hydroxylase Deficiency Allele

Open access
Tusie-Luna, Maria-Teresa, Speiser, Phyllis W., Dumic, Miro, New, Maria I., White, Perrin C.·1991·Molecular Endocrinology
DOI 10.1210/mend-5-5-685
Open this paper in CoChat — free accountOpen PDF

Abstract

The mild nonclassic form of steroid 21-hydroxylase deficiency is one of the most common autosomal recessive disorders in humans, occurring in almost 1% of caucasians and about 3% of Ashkenazi Jews. Many patients with this disorder carry a Val-281----Leu missense mutation in the CYP21 gene. This and most other mutations causing 21-hydroxylase deficiency are normally present in the CYP21P pseudogene and have presumably been transferred to CYP21 by gene conversion. To identify other potential nonclassic alleles, we used recombinant vaccinia virus to express two mutant enzymes carrying the mutations Pro-30----Leu (normally present in CYP21P) and Ser-268----Thr (considered a normal polymorphism of CYP21). Whereas the activity of the protein carrying the Ser----Thr mutation was indeed indistinguishable from the wild type, the enzyme with the Pro----Leu substitution had 60% of wild-type activity for 17-hydroxyprogesterone and about 30% of normal activity for progesterone when assayed in intact cells. When kinetic analysis of the latter mutant enzyme was performed in cellular lysates, the first order rate constants (maximum velocity/dissociation constant) for both substrates were reduced 10- to 20-fold compared with those for the wild-type enzyme. Pro-30 is conserved in many microsomal P450 enzymes and may be important for proper orientation of the enzyme with respect to the aminoterminal transmembrane segment. The Pro----Leu mutation was present in 5 of 18 patients with nonclassic 21-hydroxylase deficiency, suggesting that this mutation indeed acts as a nonclassic deficiency allele.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/mend-5-5-685

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • I172N reduces enzymatic activity to <5% of normal and is associated with the SV form of the disorder (mutation Group B).

    “( I172N)(154) reduces enzymatic activity to <5% of normal and is associated with the SV form of the disorder (mutation Group B)(107,109,221).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [107]

    In “Hybridization Analysis of Patient Samples” (page unavailable), the paper identifies I172N as a classic, severe deficiency allele in a compound heterozygote. It does not give I172N activity as <5% of normal or specifically associate it with the simple-virilizing (SV) form or mutation Group B. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Patients with P450c21 variants (e.g., the common P30L and V281L mutations and less common R339H and P453S), which have 20 to 50% of wild-type activity, can have various phenotypes, implying additional factors that can modify the clinical manifestations of 21-hydroxylase deficiency.

    “In contrast, patients with P450c21 variants [e.g., the common P30L (363) and V281L mutations and less common mutations R339H and P453S], which have 20 to 50% of wild-type activity (352, 364), can have various phenotypes, implying additional factors that can modify the clinical manifestations of 21-hydroxylase deficiency.”

    From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [363]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Gutmann I, Wahlefeld A 1983 Lactate (+)-lactate: deter- mination with lactate dehydrogenase and NAD. In: Berg- meyer HU (ed) Methods of Enzymatic Analysis, ed 2. Academic Press, New York, vol 2:1464-1468

Cited by

Sorted by citations

Related

Authors
Tusie-Luna, M.-T., Speiser, P. W., Dumic, M., New, M. I., & White, P. C.
Affiliations
Cornell University (US)
ORCID
Venue
Molecular Endocrinology
Publisher
The Endocrine Society
Published
1991-05
Volume
5
Issue
5
Pages
685-692
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
DOI
10.1210/mend-5-5-685
OpenAlex
W2120594372
Cited by
183
References
33
Citations by year
2026: 3 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 2
FWCI
2.74
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (10021)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-37867)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 00072)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
CYP21, 21-hydroxylase, gene conversion, enzyme kinetics, 17-hydroxyprogesterone, progesterone, autosomal recessive disorder, Ashkenazi Jews
MeSH terms
Adrenal Hyperplasia, Congenital, Alleles, Animals, Base Sequence, Female, Humans, Leucine, Male, Molecular Sequence Data, Mutation, Nucleic Acid Hybridization, Pedigree, Proline, Rabbits, Recombinant Proteins, Steroid 21-Hydroxylase, Vaccinia virus

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review