Submission Details

Autosomal dominant

07/19/2020

The TSHZ1 gene is located on chromosome 18 at 18q22.3 and encodes the teashirt zinc finger homeobox 1 protein. TSHZ1 is a putative zinc finger transcription factor that is expressed throughout the embryo during development (15834955: Caubit et al. 2005; 17586487: Core et al. 2007). TSHZ1 was first reported in relation to autosomal dominant congenital aural atresia in 2011 (22152683: Feenstra et al. 2011). Evidence supporting this gene-disease relationship includes case level data and experimental data. At least two variants, a stop gained variant and a frameshift variant, have been found in a heterozygous state in two individuals from one report in the literature, both with a phenotype of congenital aural atresia and hyposmia (22152683: Feenstra et al. 2011; 24487590: Ragancokova et al. 2014). Temporal and spatial expression of Tshz1 mRNA during development of the middle ear is consistent with the phenotype (17586487: Core et al. 2007). Embryos of the homozygous Tsh2 null mouse model showed a middle ear malformation as well as neonatal lethality, and a conditional nervous system-specific Tshz1 knock out mouse model demonstrated hyposmia (17586487: Core et al. 2007; 24487590: Ragancokova et al. 2014). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.

22152683 17586487 15834955 24487590