2.1. MYH9-related disorder

More than 45 mutations in the MYH9 gene have been found to cause MYH9-related disorder. This disorder is characterized by bleeding problems, hearing loss, kidney (renal) disease, and clouding of the lens of the eyes (cataracts). Most of the mutations that cause this condition change single protein building blocks (amino acids) in the myosin-9 protein. Mutations that are located near the head of the myosin protein tend to lead to a more severe disorder than mutations that are located toward the tail of the protein. Recurring mutations involving the amino acid arginine at position 702 in the protein tend to result in many problems, including a severely reduced amount of platelets (thrombocytopenia), early-onset renal disease, and hearing loss in infancy.

Mutations in the MYH9 gene lead to the production of a nonfunctional protein. A nonfunctional myosin-9 protein cannot properly interact with other subunits to form myosin IIA. Platelets, which only express myosin IIA, are most affected by a lack of functional myosin-9, accounting for the thrombocytopenia seen in all individuals with MYH9-related disorder.