title: The cardiac phenotype in patients with a CHD7 mutation.
abstract: BACKGROUND
  Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects. Heart defects are reported in 70% to 92% of patients with a CHD7 mutation, but most studies are small and do not provide a detailed classification of the defects. We present the first, detailed, descriptive study on the cardiac phenotype of 299 patients with a CHD7 mutation and discuss the role of CHD7 in cardiac development.
  
  
  RESULTS
  We collected information on congenital heart defects in 299 patients with a pathogenic CHD7 mutation, of whom 220 (74%) had a congenital heart defect. Detailed information on the heart defects was available for 202 of these patients. We classified the heart defects based on embryonic cardiac development and compared the distribution to 1007 equally classified nonsyndromic heart defects of patients registered by EUROCAT, a European Registry of Congenital Anomalies. Heart defects are highly variable in patients with CHD7 mutations, but atrioventricular septal defects and conotruncal heart defects are over-represented. Sex did not have an effect on the presence of heart defects, but truncating CHD7 mutations resulted in a heart defect significantly more often than missense or splice-site mutations (χ², P<0.001).
  
  
  CONCLUSIONS
  CHD7 plays an important role in cardiac development, given that we found a wide range of heart defects in 74% of a large cohort of patients with a CHD7 mutation. Conotruncal defects and atrioventricular septal defects are over-represented in patients with CHD7 mutations compared with patients with nonsyndromic heart defects.
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Corsten-Janssen
authors.forename: Wilhelmina S
authors.initials: WS
authors.lastname: Kerstjens-Frederikse
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: du Marchie Sarvaas
authors.forename: Maria E
authors.initials: ME
authors.lastname: Baardman
authors.forename: Marian K
authors.initials: MK
authors.lastname: Bakker
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.forename: Hanne D
authors.initials: HD
authors.lastname: Hove
authors.forename: Ketil R
authors.initials: KR
authors.lastname: Heimdal
authors.forename: Cecilie F
authors.initials: CF
authors.lastname: Rustad
authors.forename: Raoul C M
authors.initials: RC
authors.lastname: Hennekam
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Conny M A
authors.initials: CM
authors.lastname: Van Ravenswaaij-Arts
authors.forename: Livia
authors.initials: L
authors.lastname: Kapusta
mesh_terms: D015331:Cohort Studies; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000196:embryology; D006330:Heart Defects, Congenital / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D004268:DNA-Binding Proteins; D004265:DNA Helicases; C491434:CHD7 protein, human