# ANDROGEN METABOLISM IN CHILDHOOD

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 1994 · $285,414

## Abstract

The investigations described will elucidate the relationship between
clinical phenotype and molecular genotype in congenital adrenal hyperplasia
due to 21-hydroxylase deficiency (21-OHD) . Patients with each of the three
phenotypic forms i.e., salt-wasting, simple virilizing, and nonclassic
21-OHD will be categorized by detailed endocrinologic studies, and DNA
samples will be obtained from patients and family members.  In Specific Aim
1, specific alleles land genotype combinations will be identified and
correlated with each of the above-named groups.  Presence or absence of 8
functionally important mutations in the CYP21 gene encoding the active
21-hydroxylase will be analyzed by allele-specific oligonucleotide
hybridizations after amplification of genomic DNA in the polymerase chain
reaction; gene copy number will be assessed by Southern blot.  Segregation
of mutations found in individual patients will be determined by studying
parents.  De novo mutations may be identified in this manner.  Novel
mutations in CYP21 may be sought by direct sequencing of amplified DNA in
patients in whom none of the typical gene conversion mutations are found.
An attempt will be made to relate in vivo measures of 21-hydroxylase
activity, such as 17-hydroxyprogesterone and aldosterone levels, to the
degree of enzyme dysfunction as predicted from previously published in
vitro expression studies.  In Specific Aim 2, dietary sodium deprivation
will be instituted to identify patients who recover from salt-wasting.  The
ratio of plasma renin activity to aldosterone will be used as an index of
the adrenal's efficiency in producing aldosterone in patients of pre- and
post-pubertal ages.  Parallel in vitro studies will focus on
characterization of genes encoding other P450 enzymes capable of performing
steroid 21-hydroxylation in the adrenal.  Specific Aim 3 calls for
molecular genetic screening of a newborn population for the mutation found
in approximately 80% of nonclassic haplotypes bearing HLA-B14;DR1.  This
screening will both confirm the high frequency of this disorder, and allow
for study of the evolution of clinical manifestations of nonclassic 21-OHD
in the young child.  Specific Aim 4 will test the usefulness of allele--
specific hybridization in prenatal diagnosis where the CYP21 mutation is
known.  Safety and efficacy of dexamethasone prenatal treatment of
pregnancies at risk for classic 21-OHD will be assessed through careful
evaluation of complications of pregnancy and early childhood growth and
development of offspring.

## Key facts

- **NIH application ID:** 2194336
- **Project number:** 5R01HD000072-31
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **SAM.gov UEI:** YNT8TCJH8FQ8
- **Principal Investigator:** MARIA I. NEW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $285,414
- **Award type:** 5
- **Project period:** 1977-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194336

## Citation

> US National Institutes of Health, RePORTER application 2194336, ANDROGEN METABOLISM IN CHILDHOOD (5R01HD000072-31). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194336. Licensed CC0.

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