Alt. symbols: CRG | KIAA1416 | FLJ20357 | FLJ20361

Approved name: chromodomain helicase DNA binding protein 7
Alt. names: CHARGE association

Location: 8q12.2: 60678740 - 60868028 (+)
Gene type: protein_coding, 19 transcripts.

Scores: LoFtool: 0.028300 | pLI: 1.00000000 | LOEUF: 0.076

HGNC: 20626

NCBI: 55636, RefSeq: NG_007009.1

Ensembl: ENSG00000171316.14

LRG_176 | Status: public

OMIM: 608892

Expression | ProteinAtlas

CHD7 encodes a chromatin remodeling enzyme that binds enhancer elements to promote expression of target developmental genes. CHD7 plays an evolutionarily conserved role in orchestrating neural crest gene expression via key targets such as SOX9, TWIST and SLUG, and is also thought to play broader roles in regulation of cell motility (PMID: 20130577). The Wysocka lab showed that CHD7 and PBAF cooperate to promote neural crest gene expression and cell migration during embryogenesis in both humans and Xenopus (Bajpai et al., 2010). As a consequence, craniofacial bones and cartilages, the peripheral nervous system and cardiac structures are build.

Mutations in CHD7 are associated with 2 clinically overlapping autosomal dominant disorders: hypogonadotropic hypogonadism type 5 with or without anosmia [MIM:612370] and CHARGE (coloboma, heart defects, [choanal] atresia, growth retardation, genital abnormalities, and ear abnormalities) syndrome [MIM:214800]. Most commonly, CHARGE is associated with heterozygous large deletions, nonsense and frameshift mutations leading to CHD7 haploinsufficiency, though missense and splice site mutations have also been described. Many of these latter, when leading to milder or atypical CHARGE phenotypes, are now classified under hypogonadotropic hypogonadism type 5 with or without anosmia (PMID: 18834967). One report of 2 brothers with Kallmann syndrome who were heterozygous for missense mutations in CHD7 and SEMA3E also suggested the possibility of digenic inheritance (PMID: 25985275). In terms of the immune phenotype, T-cell lymphopenia is seen significantly more frequently than B- or NK- cell lymphopenia and thought secondary to thymic aplasia or hypoplasia. Patients often show increased susceptibility to infections, reduced T-cell function and hypogammaglobulinemia (PMID: 25689927, 19403480, 17684005). Wong et al. (2015) also noted in their systematic review that a significant majority of patients show diminished vaccine responses and memory, a finding recapitulated in their study from the same year (PMID: 25689927, 26544072). However, despite the absence of overt peripheral B cell defects, the latter did note that a third of their CHARGE patients had class-switched memory B-cell retaining IgM expression. Patients with CHARGE syndrome have also been reported with increased risk of atopy, reported in 65% of the patients in one study and usually presenting as food allergy (PMID: 26563674). Increased susceptibility to autoimmune disorders may also feature this syndrome but thus far have only been reported in 3 patients with Omenn-like phenotypes (PMID: 20686492, 18505430). Like for the better-characterized autoimmune predisposition in 22q11.2 deletion syndrome, it is thought that the potential development of autoimmunity in CHARGE patients might be explained by both impaired thymic and T-cell development, leading to defective nTreg generation. [Load More]