Mutation update on the CHD7 gene involved in CHARGE syndrome

Nicole Janssen, Jorieke E. H. Bergman, Morris A. Swertz, Lisbeth Tranebjaerg, Marianne Lodahl, Jeroen Schoots, Robert M. W. Hofstra, Conny M. A. van Ravenswaaij-Arts*, Lies H. Hoefsloot

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

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Abstract

CHD7 is a member of the chromodomain helicase DNA-binding (CHD) protein family that plays a role in transcription regulation by chromatin remodeling. Loss-of-function mutations in CHD7 are known to cause CHARGE syndrome, an autosomal-dominant malformation syndrome in which several organ systems, for example, the central nervous system, eye, ear, nose, and mediastinal organs, are variably involved. In this article, we review all the currently described CHD7 variants, including 183 new pathogenic mutations found by our laboratories. In total, we compiled 528 different pathogenic CHD7 alterations from 508 previously published patients with CHARGE syndrome and 294 unpublished patients analyzed by our laboratories. The mutations are equally distributed along the coding region of CHD7 and most are nonsense or frameshift mutations. Most mutations are unique, but we identified 94 recurrent mutations, predominantly arginine to stop codon mutations. We built a locus-specific database listing all the variants that is easily accessible at . In addition, we summarize the latest data on CHD7 expression studies, animal models, and functional studies, and we discuss the latest clinical insights into CHARGE syndrome. Hum Mutat 33:11491160, 2012. (c) 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)1149-1160
Number of pages12
JournalHuman Mutation
Volume33
Issue number8
DOIs
Publication statusPublished - Aug-2012

Keywords

  • CHD7
  • CHARGE syndrome
  • Kallmann syndrome
  • mutation spectrum
  • CHD7 database
  • 22Q11.2 DELETION SYNDROME
  • CONGENITAL HEART-DISEASE
  • KALLMANN-SYNDROME
  • PHENOTYPIC SPECTRUM
  • INTERSTITIAL DELETION
  • DIGEORGE-SYNDROME
  • CHOANAL ATRESIA
  • NEURAL CREST
  • MOUSE MODEL
  • MAJOR CAUSE

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