TSHZ1

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: PanelApp Australia

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: ClinGen

The TSHZ1 gene was first reported in relation to autosomal dominant congenital aural atresia/deafness in 2011 (Feenstra et al., PMID 22152683). 7 variants (missense, nonsense, frameshift) that have been reported in at least 11 probands in 3 publications (PMIDs: 22152683, 35487415, 36597107) are included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence (mouse models, expression-level evidence; PMIDs: 17586487, 24487590). Temporal and spatial expression of TSHZ1 mRNA during development of the middle ear is consistent with the phenotype (PMID: 17586487). The homozygous TSHZ1 null mouse model showed a middle ear malformation, as well as neonatal lethality. A conditional nervous system-specific TSHZ1 knock out mouse model demonstrated hyposmia (PMIDs: 17586487, 24487590). 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. This GDR was originally evaluated by the Syndromic Disorders GCEP on June 19, 2020. It was reevaluated on July 23, 2024. A new phenotype, congenital vertical talus, was reported in probands, in addition to more cases of deafness (PMIDs: 35487415, 36597107). An additional two missense variants were added to the curation from two probands in one publication (PMID: 36597107). Despite new genetic evidence, as a result of this reevaluation, the classification did not change (SOP Version 10).

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: Labcorp Genetics (formerly Invitae)

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: Illumina

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.

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: G2P

Inheritance Pattern: AD

Disease ID:MONDO:0011921

Submitter: Ambry Genetics

Inheritance Pattern: AD

Disease ID:MONDO:0008652

Submitter: Ambry Genetics