USH2A

About USH2A

USH2A on chromosome 1q41 encodes usherin, a very large protein found in the basement membranes of many tissues and at the periciliary region of photoreceptors and in the ankle link complex of the stereocilia of inner ear hair cells. Variants on both copies cause Usher syndrome type 2, the most common form of Usher syndrome, which is the leading genetic cause of combined deafness and blindness. Usher syndrome type 2 is characterized by congenital moderate to severe hearing loss, mainly affecting high frequencies, normal balance function, and retinitis pigmentosa beginning in adolescence or early adulthood. Retinitis pigmentosa causes night blindness followed by progressive loss of peripheral vision, eventually leading to tunnel vision. By comparison, Usher syndrome type 1 involves profound congenital deafness, absent vestibular function, and earlier onset retinitis pigmentosa, and type 3 involves progressive hearing loss. USH2A variants are also a common cause of non syndromic autosomal recessive retinitis pigmentosa. The syndrome is named after the British ophthalmologist Charles Usher, who emphasized its inheritance in 1914. Hearing aids and cochlear implants address hearing loss. Because the gene is too large for standard AAV vectors, RNA based exon skipping treatments and gene editing approaches have been investigated in clinical trials.