Wednesday, 13 March 2013

Usher syndrome

Usher syndrome (sometimes referred to as "Usher's syndrome") is a relatively rare genetic disorder that is associated with a mutation in any one of 10 genes resulting in a combination of hearing loss and visual impairment and is a leading cause of deafblindness. Other names for Usher syndrome include Hallgren syndrome, Usher-Hallgren syndrome, retinitis pigmentosa-dysacusis syndrome and dystrophia retinae dysacusis syndrome.Usher syndrome is incurable at present; however, using gene therapy to replace the missing gene, researchers have succeeded in reversing one form of the disease in knockout mice..

Usher syndrome I
People with Usher I are usually born deaf and often have difficulties in maintaining their balance owing to problems in the vestibular system. Babies with Usher I are usually slow to develop motor skills such as walking. Worldwide, the estimated prevalence of Usher syndrome type I is 3 to 6 per 100,000 people in the general population.

Usher syndrome type I can be caused by mutations in any one of several different genes: CDH23, MYO7A, PCDH15, USH1C, and USH1G. These genes function in the development and maintenance of inner ear structures such as hair cells (stereocilia), which transmit sound and motion signals to the brain. Alterations in these genes can cause an inability to maintain balance (vestibular dysfunction) and hearing loss. The genes also play a role in the development and stability of the retina by influencing the structure and function of both the rod photoreceptor cells and supporting cells called the retinal pigmented epithelium. Mutations that affect the normal function of these genes can result in retinitis pigmentosa and resultant vision loss.
Type I has been found to be more common in people of Ashkenazi Jewish ancestry (central and eastern European) and in the French-Acadian populations (Louisiana).

Usher syndrome II
People with Usher II are generally hard-of-hearing rather than deaf, and their hearing does not degrade over time; moreover, they generally have a normal vestibular system. Usher syndrome type II occurs at least as frequently as type I, but because type II may be underdiagnosed or more difficult to detect, it could be up to three times as common as type I.
Usher syndrome type II may be caused by mutations in any of three different genes: USH2A, GPR98 and DFNB31. The protein encoded by the USH2A gene, usherin, is located in the supportive tissue in the inner ear and retina. Usherin is critical for the proper development and maintenance of these structures, which may help explain its role in hearing and vision loss. The location and function of the other two proteins are not yet known.

Usher syndrome III
By contrast, people with Usher III experience a progressive loss of hearing and roughly half have vestibular dysfunction. The frequency of Usher syndrome type III is highest in the Finnish population, but it has been noted rarely in a few other ethnic groups.
Mutations in only one gene, the CLRN1 gene, have been linked to Usher syndrome type III. The CLRN1 gene encodes Clarin-1, a protein that is important for the development and maintenance of the inner ear and retina. However, the protein's function in these structures, and how its mutation causes hearing and vision loss, is still poorly understood.

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