title: Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions.
abstract: OBJECTIVE
  Autosomal dominant CHARGE syndrome (OMIM no. 214800) is characterized by choanal atresia or cleft lip or palate, ocular colobomas, cardiovascular malformations, retardation of growth, ear anomalies, and deafness, and is caused by mutations in the CHD7 gene. Here, we describe the outcome of a molecular genetic analysis in 18 Finnish and 56 German patients referred for molecular confirmation of the clinical diagnosis of suspected CHARGE syndrome.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction or multiplex ligation-dependent probe amplification assays did not reveal deletions in mutation negative cases, suggesting that larger CHD7 deletions are not a major cause of CHARGE syndrome.
  
  
  RESULTS
  In this group of 74 patients, we found mutations in 30 cases. 22 mutations were novel, including 11 frameshift, 5 nonsense, 3 splice-site, and 3 missense mutations. One de novo frameshift mutation was found in the last exon and is expected to result in a minimally shortened CHD7 polypeptide. Because the mutation is associated with a typical CHARGE syndrome phenotype, it may indicate the presence of an as yet unknown functional domain in the very carboxyterminal end of CHD7.
  
  
  CONCLUSIONS
  Our mutation detection rate of 40.5% is reflective of screening an unselected sample population referred for CHD7 testing based on suspected clinical diagnosis of CHARGE syndrome and not for having met strict clinical criteria for this disorder.
authors: Department of Medical Genetics, University of Turku, Turku, Finland.
authors: Pia
authors: P
authors: Vuorela
authors: Sirpa
authors: S
authors: Ala-Mello
authors: Carola
authors: C
authors: Saloranta
authors: Maila
authors: M
authors: Penttinen
authors: Minna
authors: M
authors: Pöyhönen
authors: Kirsi
authors: K
authors: Huoponen
authors: Wiktor
authors: W
authors: Borozdin
authors: Birke
authors: B
authors: Bausch
authors: Elke M
authors: EM
authors: Botzenhart
authors: Christian
authors: C
authors: Wilhelm
authors: Helena
authors: H
authors: Kääriäinen
authors: Jürgen
authors: J
authors: Kohlhase
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009154:Mutation; D016133:Polymerase Chain Reaction; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human