CHD4 is a member of the CHD gene family and encodes the chromodomain helicase DNA-binding protein 4 (CHD4), a chromatin-remodelling protein that is involved in epigenetic gene regulation (transcription), DNA damage repair and cell cycle control. CHD4 is also an important component of the NuRD complex and can, for example, interact with CHD3.

In the October issue of the American Journal of Human Genetics, an international group of researchers led by Maximilian Muenke have now reported for the first time on a causative role of CHD4 mutations in a specific congenital disorder. Using trio whole-exome sequencing, they identified de novo mutations in CHD4 in five patients. The patients presented with a recognizable clinical phenotype, showing among others distinctive facial features, macrocephaly, congenital hearing loss, developmental delay and mental retardation, and some of them additionally had congenital heart defects. Since all identified variants were missense mutations, the authors suggest that these mutations exert a specific functional effect on the NuRD complex.

Interestingly, in the September issue of Nature Genetics, Matthew Hurles and his group reported on a large study on the molecular basis of isolated and syndromic heart defects. They discovered causative variants in various genes, including disease-associated de novo mutations in CHD4 in patients with syndromic heart defects.