Submission Details

Autosomal dominant

06/25/2020

ZNF462 was first reported in relation to autosomal dominant Weiss-Kruszka syndrome in 2017 (28513610: Weiss et al. 2017). At least seven unique loss-of-function variants have been reported. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least seven probands from two publications (28513610: Weiss et al. 2017; 31361404: Kruszka et al. 2019). Majority of the variants were de novo and in one family, a variant in this gene segregated with disease in four additional family members. In one four-generation family. The mechanism for disease is heterozygous, loss of function variants. This gene-disease association is supported by expression studies that demonstrate a higher expression in fetal brain and liver, and varying expression in the brain in different developmental stages of mice. Animal models suggest that ZNF462 plays a crucial role in during vertebrate embryonic development and Zfp462+/− mice recapitulate the clinical presentation in humans (11347906: Nagase et al. 2017; 19111535: Laurent et al. 2009; 27621227: Wang et al. 2017). In summary, ZNF462 is definitively associated with autosomal dominant ZNF462-related spectrum disorder.

19111535 27621227 28513610 31361404