Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 214800 (trait) , 608892 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0008965: CHARGE syndrome

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

Mapping: From SNP-genotype data of 42 cases and 71 control half-sibs, Bourneuf et al. (2017) mapped this disorder to a 0.7Mb region on BTA14, namely 27,916,840-28,625,324, which includes the candidate causal gene CHD7. Importantly, Bourneuf et al. (2017) also showed how "Large half-sib pedigrees allow for the mapping of modifier loci in clinically variable syndromes." To this end, they identified a haplotype on a different chromosome (BTA24: 29,068,445-29,893,427) that "has a major positive effect on the clinical presentation of" this disorder in cattle and, by homology, to its human homologue, CHARGE syndrome. The utility of this strategy was confirmed when it was discovered that this haplotype includes "CDH2, which is a target of the CHD7 transcription factor".

Molecular basis: Bourneuf et al. (2017): a de novo likely causal variant is the frameshift variant p.K594AfsX29

Clinical features: Bourneuf et al. (2017): "hypotonia . . . , lack of balance and coordination in the days following birth, facial abnormalities, heart defects and growth delay"

Breed: Montbéliarde (Cattle) (VBO_0000306).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: