Dr. Friedman noted, "Using DNA contributions from affected families in the United States and Israel, we searched for a haplotype of genetic markers closely linked to any of six reported USH1 loci in families of Ashkenazi Jewish descent."
This approach allowed identification of the R245X founder mutation. They found high carrier frequencies of R245X in the Ashkenazi Jewish population. Carriers are individuals who, although having no symptoms of the disorder, transmit their single copy of the disabled gene to their descendants.
There are no data to indicate that there is an increased frequency of Usher syndrome in this population, only that the inheritance of the disorder is more clearly identifiable. There is indication, through the study's controls of other non-Ashkenazi Jewish and non-Jewish populations, that this mutation may be unique to the Ashkenazi population.
Uncovering the R245X mutation as a significant cause of USH1 in Ashkenazi Jewish individuals, means there are diagnostic and intervention strategies that can be helpful in ameliorating the devastation of this disorder.
"Knowledge is truly empowerment in this case," noted James F. Battey, M.D., Ph.D., Director of the National Institute on Deafness and Other Communication Disorders. "Molecular diagnosis, carrier screening, and genetic counseling all will lead to earlier intervention for a child who will be challenged by hearing loss and progressive blindness, while he or she can still take advantage of the sensory input still available in the earlier years."
Molecular screening is an important tool for use with children in this population, who are born with bilateral, profound hearing loss, not associated with GJB2 mutations. From these finding, it has become clear that these children should be tested for R245X and have ophthalmologic
evaluation, including funduscopic examination and electroretinography.
Contact: Marin P. Allen, Ph.D.
NIH/National Institute on Deafness and Other Communication Disorders