# GENE MUTATION IN 21-HYDROXYLASE DEFICIENCY

> **NIH NIH K11** · CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS · 1994 · $93,420

## Abstract

All forms of 21-hydroxylase deficiency, salt-losing, simple virilizing, and
late-onset, share a common gene locus (CYP21B) in the class III region of
the major histocompatibility complex on chromosome 6 in tandem duplication
with a pseudogene (CYP21A).  Gene deletions, conversions, and point
mutations have been described in patients with 21-hydroxylase deficiency.
This heterogeneity of clinical phenotypes and mutational events suggests
that there is a wide variation in the expression of 21-hydroxylase
activity.

To evaluate our hypothesis that greater disturbance of gene expression
leads to greater decrease in 21-hydroxylase activity manifested as more
severe phenotypic disease, we propose to correlate ,the frequency of
alterations in the structural portion of the 21-hydroxylase gene, detected
through genomic DNA amplification utilizing polymerase chain reaction and
dot-blot analysis, with the clinical phenotype, clinical severity and
17-hydroxyprogesterone response to synthetic ACTH, in our population of
affected families Since defects may occur in the regulatory portion of the
gene, we will examine the regulatory portion if there are no apparent
nucleotide sequence alterations in the structural portion of the gene.

To confirm that detected sequence alterations affect enzyme activity,
expression of the altered sequence in pKCRH-2 transfected into COS-7 monkey
kidney cells with determination of conversion of
17-hydroxy[14C]progesterone into 14C-lldeoxycortisol will be performed.
Results of expressed enzyme activity will be correlated with phenotype and
genotype to determine if phenotype predicts genotype.

## Key facts

- **NIH application ID:** 2194431
- **Project number:** 5K11HD000965-03
- **Recipient organization:** CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
- **SAM.gov UEI:** K9M2PLP2T7H1
- **Principal Investigator:** SELMA FELDMAN WITCHEL
- **Activity code:** K11 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $93,420
- **Award type:** 5
- **Project period:** 1992-04-01 → 1997-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194431

## Citation

> US National Institutes of Health, RePORTER application 2194431, GENE MUTATION IN 21-HYDROXYLASE DEFICIENCY (5K11HD000965-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194431. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*