Usher syndrome

Usher syndrome is a rare genetic disorder that causes a combination of hearing loss, progressive vision loss, and in some cases, balance problems. It is the most common condition that affects both hearing and vision. Usher syndrome missense mutations can lead to proteopathies that result in the misfolding of the protein and targeted removal by endoplasmic reticulum associated degradation (ERAD) facilitated by ubiquitin. One example is the Ashkenazi form of Usher Type 3A, a recessive rare genetic disease of progressive hearing and vision loss caused by a single point mutation in the Clarin1 gene. This mutation causes a single amino acid substitution in the Clarin1 protein leading to improper protein folding and ERAD. Another example of Usher Type 3A is the Finnish mutation (Y176X), which leads to a truncation of Clarin1 and no protein production. At present, there are no FDA-approved therapies that cure or directly treat the underlying cause of Usher syndrome.