Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism

Yuko Nakayama, Fredric Wondisford, Robert W. Lash, Allen E. Bale, Bruce D. Weintraub, Gordon B. Cutler, Sally Radovick

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHl digests revealed 6.5- and 2.7-kilobase (kb) bands; Bglll, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; Xbal, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hy-pogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with Ncol, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon-intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the −8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5′ flanking region or the four exons and their splice sites.

Original languageEnglish (US)
Pages (from-to)1233-1238
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume70
Issue number5
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

Gonadotropin-Releasing Hormone
Genes
Polymorphism
Exons
Nucleotides
5' Flanking Region
Polymerase chain reaction
Protein Sorting Signals
Reaction products
Tryptophan
Introns
Serine
Southern Blotting
Sexual precocity
Idiopathic Hypogonadotropic Hypogonadism
Central Precocious Puberty
Complementary DNA
Digestion
Amino Acids
DNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

@article{bc737ba4c7fb45a2bf21275a7e196928,
title = "Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism",
abstract = "We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHl digests revealed 6.5- and 2.7-kilobase (kb) bands; Bglll, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; Xbal, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hy-pogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with Ncol, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon-intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the −8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5′ flanking region or the four exons and their splice sites.",
author = "Yuko Nakayama and Fredric Wondisford and Lash, {Robert W.} and Bale, {Allen E.} and Weintraub, {Bruce D.} and Cutler, {Gordon B.} and Sally Radovick",
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Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism. / Nakayama, Yuko; Wondisford, Fredric; Lash, Robert W.; Bale, Allen E.; Weintraub, Bruce D.; Cutler, Gordon B.; Radovick, Sally.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 70, No. 5, 01.01.1990, p. 1233-1238.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism

AU - Nakayama, Yuko

AU - Wondisford, Fredric

AU - Lash, Robert W.

AU - Bale, Allen E.

AU - Weintraub, Bruce D.

AU - Cutler, Gordon B.

AU - Radovick, Sally

PY - 1990/1/1

Y1 - 1990/1/1

N2 - We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHl digests revealed 6.5- and 2.7-kilobase (kb) bands; Bglll, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; Xbal, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hy-pogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with Ncol, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon-intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the −8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5′ flanking region or the four exons and their splice sites.

AB - We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHl digests revealed 6.5- and 2.7-kilobase (kb) bands; Bglll, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; Xbal, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hy-pogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with Ncol, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon-intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the −8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5′ flanking region or the four exons and their splice sites.

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