COLLABORATIVE STUDY OF USHER SYNDROME

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.