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.
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Georgia Health Sciences University, Augusta, GA 30912, United States.
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D000818:Animals; D058747:CHARGE Syndrome / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000235:genetics*; D017436:Kallmann Syndrome / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D004265:DNA Helicases; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C435527:WDR11 protein, human; D000092468:Bromodomain Containing Proteins; C491434:CHD7 protein, human