Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene

Michael J. McPhaul, Marco Marcelli, Sonia Zoppi, Carol M. Wilson, Jim Griffin III, Jean D. Wilson

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminisation, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for ∼ 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-β) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.

Original languageEnglish (US)
Pages (from-to)2097-2101
Number of pages5
JournalJournal of Clinical Investigation
Volume90
Issue number5
StatePublished - Nov 1992

Fingerprint

Androgen Receptors
Androgen-Insensitivity Syndrome
Multigene Family
Ligands
Mutation
Hormones
Genes
Thyroid Hormone Resistance Syndrome
Amino Acids
Thyroid Hormone Receptors
Fibroblasts
Phenotype
Skin

Keywords

  • Androgen
  • Mutation
  • Receptor
  • Resistance
  • Steroid

ASJC Scopus subject areas

  • Medicine(all)

Cite this

McPhaul, M. J., Marcelli, M., Zoppi, S., Wilson, C. M., Griffin III, J., & Wilson, J. D. (1992). Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. Journal of Clinical Investigation, 90(5), 2097-2101.

Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. / McPhaul, Michael J.; Marcelli, Marco; Zoppi, Sonia; Wilson, Carol M.; Griffin III, Jim; Wilson, Jean D.

In: Journal of Clinical Investigation, Vol. 90, No. 5, 11.1992, p. 2097-2101.

Research output: Contribution to journalArticle

McPhaul, MJ, Marcelli, M, Zoppi, S, Wilson, CM, Griffin III, J & Wilson, JD 1992, 'Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene', Journal of Clinical Investigation, vol. 90, no. 5, pp. 2097-2101.
McPhaul, Michael J. ; Marcelli, Marco ; Zoppi, Sonia ; Wilson, Carol M. ; Griffin III, Jim ; Wilson, Jean D. / Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. In: Journal of Clinical Investigation. 1992 ; Vol. 90, No. 5. pp. 2097-2101.
@article{56318cd13f1140aa83c829b9868bf606,
title = "Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene",
abstract = "We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminisation, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90{\%}) cluster in two regions that account for ∼ 35{\%} of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-β) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.",
keywords = "Androgen, Mutation, Receptor, Resistance, Steroid",
author = "McPhaul, {Michael J.} and Marco Marcelli and Sonia Zoppi and Wilson, {Carol M.} and {Griffin III}, Jim and Wilson, {Jean D.}",
year = "1992",
month = "11",
language = "English (US)",
volume = "90",
pages = "2097--2101",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene

AU - McPhaul, Michael J.

AU - Marcelli, Marco

AU - Zoppi, Sonia

AU - Wilson, Carol M.

AU - Griffin III, Jim

AU - Wilson, Jean D.

PY - 1992/11

Y1 - 1992/11

N2 - We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminisation, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for ∼ 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-β) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.

AB - We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminisation, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for ∼ 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-β) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.

KW - Androgen

KW - Mutation

KW - Receptor

KW - Resistance

KW - Steroid

UR - http://www.scopus.com/inward/record.url?scp=0026483082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026483082&partnerID=8YFLogxK

M3 - Article

C2 - 1430233

AN - SCOPUS:0026483082

VL - 90

SP - 2097

EP - 2101

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -