Mutation update on the CHD7 gene involved in CHARGE syndrome

TY - JOUR

T1 - Mutation update on the CHD7 gene involved in CHARGE syndrome

AU - Janssen, Nicole

AU - Bergman, Jorieke E H

AU - Swertz, Morris A

AU - Tranebjaerg, Lisbeth

AU - Lodahl, Marianne

AU - Schoots, Jeroen

AU - Hofstra, Robert M W

AU - van Ravenswaaij-Arts, Conny M A

AU - Hoefsloot, Lies H

N1 - © 2012 Wiley Periodicals, Inc.

PY - 2012/8

Y1 - 2012/8

N2 - 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compiled 528 different pathogenic CHD7 alterations from 508 previously published patients with CHARGE syndrome and 294 unpublished patients analyzed by our laboratories.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.

AB - 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compiled 528 different pathogenic CHD7 alterations from 508 previously published patients with CHARGE syndrome and 294 unpublished patients analyzed by our laboratories.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.

U2 - 10.1002/humu.22086

DO - 10.1002/humu.22086

M3 - Journal article

C2 - 22461308

SN - 1059-7794

VL - 33

SP - 1149

EP - 1160

JO - Human Mutation

JF - Human Mutation

IS - 8

ER -