Submission Details

Autosomal dominant

01/23/2020

The FHOD3 gene is located on chromosome 18 at 18q12.2 and encodes the formin homology 2 domain containing 3, which is associated with actin organization. The FHOD3 gene was first reported in relation to autosomal dominant hypertrophic cardiomyopathy in 2018 (30442288: Ochoa et al. 2018). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least five unrelated probands in two publications (30442288: Ochoa et al. 2018; 31742804: Huang et al. 2019). Variants in this gene segregated with disease in one large seven-generation family and in multiple nuclear families (30442288: Ochoa et al. 2018). The mechanism of disease has not been clearly defined, but both missense and in-frame deletion variants have been associated with disease (30442288: Ochoa et al. 2018; 31742804: Huang et al. 2019). This gene-disease relationship is supported by expression data in the developing heart and sarcomeres and functional alteration in non-patient cells demonstrating impaired myofibril maintenance and defective polymerization of actin filaments in cardiomyocytes (21149568: Iskratsch et al. 2010; 26848968: Fujimoto et al. 2016). Rescue experiments in cultured cardiomyocytes and a transgenic mouse line also support a role for FHOD3 in the developing sarcomere (19706596: Taniguchi et al. 2009; 26848968: Fujimoto et al. 2016). 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.

30442288 31742804 26848968 21149568 19706596