Usher Syndrome is a disorder characterized by congenital hearing loss with progressive retinitis pigmentosa. It is inherited as an autosomal recessive. Clinical variation between families has led investigators to hypothesize the existence of different subtypes which may reflect on underlying genetic heterogeneity. We are proposing a genetic study whose main objective is to localize the gene which causes Type I Usher Syndrome. Usher Syndrome Type I (profound deafness, vestibular dysfunction, and retinitis pigmentosa) is the most common type of Usher Syndrome, comprising between 60 and 90% of all cases. At least 100 families, each with two or more affected siblings, are to be collected. Approximately 50 families will come to BTNRH for in-depth clinical studies. An additional 50 families will be seen in Sweden of which about 30 were in Hallgren's original study published in 1959. Lymphocytes from all informative families will be immortalized by transformation and made freely available to other investigators. In depth clinical evaluations which will be done both in the USA and Sweden will include complete vestibular, audiological, ophthalmologic and genetic studies. Families will be studied for linkage using a large battery of classical and DNA polymorphisms. A method of interval mapping will be used to maximize the likelihood of finding linkage and to improve the chance of finding heterogeneity if it exists. Since Usher Syndrome results in the loss of the two most vital human senses, the burden to patients with this disorder is tremendous. It acts to isolate them from the rest of society and reduces their ability to act independently. About 1 out of 20,000 individuals is affected with Usher Syndrome. However, as many as 5% of all congenitally deaf are affected. Thus, Usher Syndrome is one of the major problems facing researchers in deafness. Answers to questions regarding the etiology of Usher Syndrome will have important implications in the field of communicative disorders and better understanding of its underlying etiology may lead to more effective genetic counseling and treatment.
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| Astuto, L M; Bork, J M; Weston, M D et al. (2002) CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness. Am J Hum Genet 71:262-75 |
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| Orten, D J; Weston, M D; Kelley, P M et al. (1999) Analysis of DNA elements that modulate myosin VIIA expression in humans. Hum Mutat 14:354 |
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