Submission Details

Autosomal dominant

03/07/2019

The WNT5A gene is located on chromosome 3 at 3p14.3 and encodes Wnt family member 5A, which is a ligand for members of the frizzled family of seven transmembrane receptors and is involved in both the canonical and noncanonical signaling pathways, depending upon the receptor context. WNT proteins play an essential role during development, controlling processes such as embryonic patterning, cell growth, migration, and differentiation. The WNT5A gene was first reported in relation to autosomal dominant Robinow syndrome in 2010 (19918918: Person et al. 2010). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least eight probands in four publications (19918918: Person et al. 2010; 24716670: Roifman et al. 2015; 27092434: Xiong et al. 2016; 29276006: White et al. 2018). Variants in this gene segregated with disease in approximately nine additional family members. The mechanism of disease has not been clearly defined, but missense variants were most commonly reported, and functional data for two suggested they were hypomorphic (19918918: Person et al. 2010). This gene-disease relationship is supported by expression and biochemical function data as well as a knock out mouse model (10021340: Yamaguchi et al. 1999; 12839624: Oishi et al. 2003; 16602827: Mikels and Nusse 2006). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged.

24716670 27092434 19918918 12839624 16602827 10021340 29276006