title: The results of CHD7 analysis in clinically well-characterized patients with Kallmann syndrome.
abstract: BACKGROUND
  Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a minority of KS patients.
  
  
  OBJECTIVE
  We aimed to investigate whether CHD7 mutations can give rise to isolated KS or whether additional features of CHARGE syndrome always occur.
  
  
  METHODS
  We performed CHD7 analysis in a cohort of 36 clinically well-characterized Dutch patients with KS but without mutations in KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1, PROK2, PROKR2, and FGF8.
  
  
  RESULTS
  We identified three heterozygous CHD7 mutations. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome.
  
  
  CONCLUSIONS
  The yield of CHD7 analysis in patients with isolated KS seems very low but increases when additional CHARGE features are present. Therefore, we recommend performing CHD7 analysis in KS patients who have at least two additional CHARGE features or semicircular canal anomalies. Identifying a CHD7 mutation has important clinical implications for the surveillance and genetic counseling of patients.
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.forename: Willem
authors.initials: W
authors.lastname: de Ronde
authors.forename: Marjolijn C J
authors.initials: MC
authors.lastname: Jongmans
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.forename: Sten L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Ad
authors.initials: A
authors.lastname: Hermus
authors.forename: Gianni
authors.initials: G
authors.lastname: Bocca
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
mesh_terms: D000328:Adult; D058747:CHARGE Syndrome / Q000235:genetics; D015331:Cohort Studies; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human