| Locus (OMIM) | Gene (OMIM) | Inheritance | Key Locus References (PubMed) | Key Gene References (PubMed) | Evidence (ClinGen)  |
|---|---|---|---|---|---|
| ATS1 | COL4A5 | X-linked Dominant | Menlove et al., 1984; Atkin et al., 1988 | Barker et al., 1990 | Definitive |
| ATS2 | COL4A4 | Autosomal Recessive | Mochizuki et al., 1994 | Mochizuki et al., 1994 | Definitive |
| ATS3A | COL4A3 | Autosomal Dominant | Jefferson et al., 1997 | Jefferson et al., 1997 | Definitive |
| ATS3B | COL4A3 | Autosomal Recessive | Mochizuki et al., 1994 | Mochizuki et al., 1994 | Definitive |
The molecular composition of the extensive basement membranes structures in the cochlea is varied and specific, and changes in the component proteins can lead to sensorineural hearing loss. To date, these changes have been associated with disease in other organ systems as well, resulting in syndromic hearing loss. Alport syndrome is the classic example. It is caused by mutations in COL4A3, COL4A4 or COL4A5. These collagens have a more restricted tissue distribution than either COL4A1 or COL4A2, the most common and ubiquitous of the basement membrane collagens. COL4A3, COL4A4 and COL4A5 are found in the basilar membrane, parts of the spiral ligament, and stria vascularis. Although the mechanism of hearing loss is not known, in the glomerulus there is focal thinning and thickening with eventual basement membrane splitting. Extrapolating to the ear, in the spiral sulcus, loss of integrity of the basement membrane might affect adhesion of the tectorial membrane, and in the basilar membrane and its junction with the spiral ligament, translation of mechanical energy may be affected (Cosgrove et al., 1996).