CoChat
Sign Up
Cited by 2,471Estrogen and related hormone effectsSexual Differentiation and DisordersGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man

Open access
Smith, Eric P., Boyd, Jeff, Frank, Graeme R., Takahashi, Hiroyuki, Cohen, Robert M., Specker, Bonny, Williams, Timothy C., Lubahn, Dennis B., Korach, Kenneth S.·1994·New England Journal of Medicine
DOI 10.1056/nejm199410203311604
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND AND METHODS: Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing. RESULTS: The patient was tall (204 cm [80.3 in.]) and had incomplete epiphyseal closure, with a history of continued linear growth into adulthood despite otherwise normal pubertal development. He was normally masculinized and had bilateral axillary acanthosis nigricans. Serum estradiol and estrone concentrations were elevated, and serum testosterone concentrations were normal. Serum follicle-stimulating hormone and luteinizing hormone concentrations were increased. Glucose tolerance was impaired, and hyperinsulinemia was present. The bone mineral density of the lumbar spine was 0.745 g per square centimeter, 3.1 SD below the mean for age-matched normal women; there was biochemical evidence of increased bone turnover. The patient had no detectable response to estrogen administration, despite a 10-fold increase in the serum free estradiol concentration. Conformation analysis of his estrogen-receptor gene revealed a variant banding pattern in exon 2. Direct sequencing of exon 2 revealed a cytosine-to-thymine transition at codon 157 of both alleles, resulting in a premature stop codon. The patient's parents were heterozygous carriers of this mutation, and pedigree analysis revealed consanguinity. CONCLUSIONS: Disruption of the estrogen receptor in humans need not be lethal. Estrogen is important for bone maturation and mineralization in men as well as women.

Overview

Integrity signals

Registry

Crossref · 10.1056/nejm199410203311604

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Citations

Cites

Show all 30 references

Research works printed but not linked: 3

  1. Valenta LJ, 1992, J Natl Med Assoc, 84, 241
  2. Swartz CM, 1988, N Engl J Med, 318, 996
  3. Sharp SC, 1993, Diabetes Rev, 1, 318

Cited by

Sorted by citations

See all 2,471

Related

Metadata

Authors
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • National Institutes of Health (US)
  • University of North Carolina at Chapel Hill (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1994-10-20
Volume
331
Issue
16
Pages
1056-1061
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199410203311604
OpenAlex
W2321613759
Cited by
2,471
References
30
Citations by year
2026: 18 · 2025: 26 · 2024: 22 · 2023: 32 · 2022: 36 · 2021: 42 · 2020: 49 · 2019: 55 · 2018: 59 · 2017: 60 · 2016: 60 · 2015: 70 · 2014: 76 · 2013: 72 · 2012: 67
FWCI
35.15
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Center for Research Resources (M01RR008084, MO1 RR 08084)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Keywords
estrogen resistance, estrogen receptor gene, estrogen receptor mutations, premature stop codon, pituitary-gonadal function, hyperinsulinemia, impaired glucose tolerance, bone mineral density, bone turnover, epiphyseal closure, consanguinity, transdermal estrogen, tall stature
MeSH terms
Adult, Base Sequence, Codon, Drug Resistance, Estrogens, Humans, Male, Molecular Sequence Data, Mutation, Osteoporosis, Pedigree, Receptors, Estrogen, Polymerase Chain Reaction

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