Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor

K. Imasaki, Tomonobu Hasegawa, H. Ishizaka, T. Okabe, Y. Hasegawa, R. Takayanagi, H. Nawata

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have analyzed the androgen receptor (AR) of a young Japanese man with sporadic Reifenstein syndrome. Androgen binding assays in cultured genital skin fibroblasts showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts decreased to 37% when the assay temperature was raised from 30°C to 41°C, indicating thermolability of the AR. Sequence analysis of the AR gene revealed a single nucleotide substitution (G→A) at nucleotide position 2,598 in exon E (or 5), resulting in conversion of valine (GTG) to methionine (ATG) at amino acid position 746 within the hormone-binding domain of the AR. This missense mutation may explain thermolability of the AR, which is thought to be the pathogenesis of Reifenstein syndrome in this patient. Sequence analysis also revealed that his mother was not a heterozygous carrier of this AR mutation. Moreover, sequence analysis of the D loop in the mitochondrial deoxyribonuleic acid (DNA) confirmed the familial relationship between this patient and his mother. These findings strongly suggest that this AR mutation is a de novo mutation newly occurring in this patient's generation.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalClinical Pediatric Endocrinology
Volume5
Issue number1
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Androgen-Insensitivity Syndrome
Androgen Receptors
Mutation
Sequence Analysis
Androgens
Nucleotides
Fibroblasts
Mothers
Valine
Missense Mutation
Methionine
Exons
Hormones
Amino Acids
Skin
Temperature
Acids

Keywords

  • Androgen insensitivity syndrome
  • Androgen receptor
  • De novo mutation
  • Missense mutation
  • Reifenstein syndrome
  • Thermolability

ASJC Scopus subject areas

  • Endocrinology
  • Pediatrics, Perinatology, and Child Health

Cite this

Imasaki, K., Hasegawa, T., Ishizaka, H., Okabe, T., Hasegawa, Y., Takayanagi, R., & Nawata, H. (1996). Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor. Clinical Pediatric Endocrinology, 5(1), 1-9.

Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor. / Imasaki, K.; Hasegawa, Tomonobu; Ishizaka, H.; Okabe, T.; Hasegawa, Y.; Takayanagi, R.; Nawata, H.

In: Clinical Pediatric Endocrinology, Vol. 5, No. 1, 1996, p. 1-9.

Research output: Contribution to journalArticle

Imasaki, K, Hasegawa, T, Ishizaka, H, Okabe, T, Hasegawa, Y, Takayanagi, R & Nawata, H 1996, 'Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor', Clinical Pediatric Endocrinology, vol. 5, no. 1, pp. 1-9.
Imasaki, K. ; Hasegawa, Tomonobu ; Ishizaka, H. ; Okabe, T. ; Hasegawa, Y. ; Takayanagi, R. ; Nawata, H. / Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor. In: Clinical Pediatric Endocrinology. 1996 ; Vol. 5, No. 1. pp. 1-9.
@article{b98262865a084ad68376311fe6566e96,
title = "Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor",
abstract = "We have analyzed the androgen receptor (AR) of a young Japanese man with sporadic Reifenstein syndrome. Androgen binding assays in cultured genital skin fibroblasts showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts decreased to 37{\%} when the assay temperature was raised from 30°C to 41°C, indicating thermolability of the AR. Sequence analysis of the AR gene revealed a single nucleotide substitution (G→A) at nucleotide position 2,598 in exon E (or 5), resulting in conversion of valine (GTG) to methionine (ATG) at amino acid position 746 within the hormone-binding domain of the AR. This missense mutation may explain thermolability of the AR, which is thought to be the pathogenesis of Reifenstein syndrome in this patient. Sequence analysis also revealed that his mother was not a heterozygous carrier of this AR mutation. Moreover, sequence analysis of the D loop in the mitochondrial deoxyribonuleic acid (DNA) confirmed the familial relationship between this patient and his mother. These findings strongly suggest that this AR mutation is a de novo mutation newly occurring in this patient's generation.",
keywords = "Androgen insensitivity syndrome, Androgen receptor, De novo mutation, Missense mutation, Reifenstein syndrome, Thermolability",
author = "K. Imasaki and Tomonobu Hasegawa and H. Ishizaka and T. Okabe and Y. Hasegawa and R. Takayanagi and H. Nawata",
year = "1996",
language = "English",
volume = "5",
pages = "1--9",
journal = "Clinical Pediatric Endocrinology",
issn = "0918-5739",
publisher = "Jeff Corporation Co. Ltd",
number = "1",

}

TY - JOUR

T1 - Sporadic Reifenstein syndrome due to a de novo mutation (746Val→Met) of the androgen receptor

AU - Imasaki, K.

AU - Hasegawa, Tomonobu

AU - Ishizaka, H.

AU - Okabe, T.

AU - Hasegawa, Y.

AU - Takayanagi, R.

AU - Nawata, H.

PY - 1996

Y1 - 1996

N2 - We have analyzed the androgen receptor (AR) of a young Japanese man with sporadic Reifenstein syndrome. Androgen binding assays in cultured genital skin fibroblasts showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts decreased to 37% when the assay temperature was raised from 30°C to 41°C, indicating thermolability of the AR. Sequence analysis of the AR gene revealed a single nucleotide substitution (G→A) at nucleotide position 2,598 in exon E (or 5), resulting in conversion of valine (GTG) to methionine (ATG) at amino acid position 746 within the hormone-binding domain of the AR. This missense mutation may explain thermolability of the AR, which is thought to be the pathogenesis of Reifenstein syndrome in this patient. Sequence analysis also revealed that his mother was not a heterozygous carrier of this AR mutation. Moreover, sequence analysis of the D loop in the mitochondrial deoxyribonuleic acid (DNA) confirmed the familial relationship between this patient and his mother. These findings strongly suggest that this AR mutation is a de novo mutation newly occurring in this patient's generation.

AB - We have analyzed the androgen receptor (AR) of a young Japanese man with sporadic Reifenstein syndrome. Androgen binding assays in cultured genital skin fibroblasts showed a normal maximum binding capacity and a normal apparent dissociation constant. However, androgen binding in fibroblasts decreased to 37% when the assay temperature was raised from 30°C to 41°C, indicating thermolability of the AR. Sequence analysis of the AR gene revealed a single nucleotide substitution (G→A) at nucleotide position 2,598 in exon E (or 5), resulting in conversion of valine (GTG) to methionine (ATG) at amino acid position 746 within the hormone-binding domain of the AR. This missense mutation may explain thermolability of the AR, which is thought to be the pathogenesis of Reifenstein syndrome in this patient. Sequence analysis also revealed that his mother was not a heterozygous carrier of this AR mutation. Moreover, sequence analysis of the D loop in the mitochondrial deoxyribonuleic acid (DNA) confirmed the familial relationship between this patient and his mother. These findings strongly suggest that this AR mutation is a de novo mutation newly occurring in this patient's generation.

KW - Androgen insensitivity syndrome

KW - Androgen receptor

KW - De novo mutation

KW - Missense mutation

KW - Reifenstein syndrome

KW - Thermolability

UR - http://www.scopus.com/inward/record.url?scp=0030317767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030317767&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0030317767

VL - 5

SP - 1

EP - 9

JO - Clinical Pediatric Endocrinology

JF - Clinical Pediatric Endocrinology

SN - 0918-5739

IS - 1

ER -