The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

Hyung Goo Kim, Lawrence C Layman

Research output: Contribution to journalReview article

27 Citations (Scopus)

Abstract

Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE syndrome, which includes eye coloboma, heart malformations, atresia of the choanae, retardation of growth/development, genital anomalies, and ear abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal dominant. CHD7 encodes a large protein that participates in chromatin remodeling and transcription. Findings from studies of mouse models employing ENU-mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE patients may manifest anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features. Therefore, it has been hypothesized that IHH/KS represents a milder allelic variant of CHARGE syndrome, which has been supported by the identification of heterozygous CHD7 mutations in both normosmic IHH and KS. Developmental expression within the hypothalamus and the presence of human mutations indicate that CHD7 has an important role in puberty and reproduction. In addition, WDR11 was recently identified by positional cloning; and mutations in were identified in IHH/KS patients, suggesting a role for this gene in normal puberty.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume346
Issue number1-2
DOIs
StatePublished - Oct 22 2011

Fingerprint

Kallmann Syndrome
CHARGE Syndrome
DNA-Binding Proteins
Genes
Mutation
Puberty
Mutagenesis
Cloning
Olfaction Disorders
Coloboma
Transcription
Chromatin Assembly and Disassembly
Hypogonadism
Nasopharynx
Congenital Heart Defects
Chromatin
Growth and Development
Hypothalamus
Reproduction
Ear

Keywords

  • Anosmia
  • CHARGE syndrome
  • CHD7 gene
  • GnRH neuron
  • Idiopathic hypogonadotropic hypogonadism
  • Kallmann syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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title = "The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome",
abstract = "Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE syndrome, which includes eye coloboma, heart malformations, atresia of the choanae, retardation of growth/development, genital anomalies, and ear abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal dominant. CHD7 encodes a large protein that participates in chromatin remodeling and transcription. Findings from studies of mouse models employing ENU-mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE patients may manifest anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features. Therefore, it has been hypothesized that IHH/KS represents a milder allelic variant of CHARGE syndrome, which has been supported by the identification of heterozygous CHD7 mutations in both normosmic IHH and KS. Developmental expression within the hypothalamus and the presence of human mutations indicate that CHD7 has an important role in puberty and reproduction. In addition, WDR11 was recently identified by positional cloning; and mutations in were identified in IHH/KS patients, suggesting a role for this gene in normal puberty.",
keywords = "Anosmia, CHARGE syndrome, CHD7 gene, GnRH neuron, Idiopathic hypogonadotropic hypogonadism, Kallmann syndrome",
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T1 - The role of CHD7 and the newly identified WDR11 gene in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome

AU - Kim, Hyung Goo

AU - Layman, Lawrence C

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N2 - Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE syndrome, which includes eye coloboma, heart malformations, atresia of the choanae, retardation of growth/development, genital anomalies, and ear abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal dominant. CHD7 encodes a large protein that participates in chromatin remodeling and transcription. Findings from studies of mouse models employing ENU-mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE patients may manifest anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features. Therefore, it has been hypothesized that IHH/KS represents a milder allelic variant of CHARGE syndrome, which has been supported by the identification of heterozygous CHD7 mutations in both normosmic IHH and KS. Developmental expression within the hypothalamus and the presence of human mutations indicate that CHD7 has an important role in puberty and reproduction. In addition, WDR11 was recently identified by positional cloning; and mutations in were identified in IHH/KS patients, suggesting a role for this gene in normal puberty.

AB - Mutations in the chromodomain helicase DNA binding protein-7 (CHD7) cause CHARGE syndrome, which includes eye coloboma, heart malformations, atresia of the choanae, retardation of growth/development, genital anomalies, and ear abnormalities. CHARGE syndrome is usually sporadic, but is also autosomal dominant. CHD7 encodes a large protein that participates in chromatin remodeling and transcription. Findings from studies of mouse models employing ENU-mutagenesis or gene-trap methods recapitulate human CHARGE syndrome. CHARGE patients may manifest anosmia and/or hypogonadism, features that overlap with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Similarly, IHH/KS patients may also display partial CHARGE features. Therefore, it has been hypothesized that IHH/KS represents a milder allelic variant of CHARGE syndrome, which has been supported by the identification of heterozygous CHD7 mutations in both normosmic IHH and KS. Developmental expression within the hypothalamus and the presence of human mutations indicate that CHD7 has an important role in puberty and reproduction. In addition, WDR11 was recently identified by positional cloning; and mutations in were identified in IHH/KS patients, suggesting a role for this gene in normal puberty.

KW - Anosmia

KW - CHARGE syndrome

KW - CHD7 gene

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KW - Idiopathic hypogonadotropic hypogonadism

KW - Kallmann syndrome

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