Finnish Common Mutation for Usher Syndrome (Tyr176X in CLRN1) Test Details
Usher syndrome represents the most common type of autosomal recessive syndromic hearing loss and is the most common genetic cause of combined deafness and blindness. One founder mutation that is causative for Usher syndrome has been identified in the Finnish population: Tyr176X variant in the CLRN1 gene.Read More...
Usher syndrome is subdivided into three clinical types depending on the severity and onset of hearing impairment, retinitis pigmentosa (RP), as well as the presence of a vestibular dysfunction. Usher Syndrome Type 3 is characterized by later onset hearing loss, variable vestibular dysfunction and RP that can present between the second and fourth decade of life. To date, only pathogenic variants in the CLRN1 (USH3A) gene are known to be causative for this type of Usher Syndrome.
Usher syndrome due to pathogenic variants in the CLRN1 gene is inherited in an autosomal recessive manner. An individual would need to inherit two pathogenic variants in order to have clinical features. Two carriers have a 25% (or 1 in 4) chance of each passing on a pathogenic variant and having a child with hearing loss related to Usher syndrome.Less
Individuals of Finnish descent who were born with hearing loss, of any severity, are candidates for the Finnish Common Mutation Test. This is true even if there is no family history of hearing loss, as this is the most common presentation. The Finnish Common Mutation Test can also be used for carrier screening and family planning. However, this test is variant specific and cannot rule out causes or risks of hearing loss due to other variants within the CLRN1 gene or other genes not covered by this test.
This test is performed by Sanger sequencing of exon 3 of the CLRN1 gene. This test does not detect large deletions or variants in regions and genes not covered by this test.
Analytical and Clinical Sensitivity
This test is greater than 99.9% accurate in detecting variants in the sequence analyzed. Carrier frequency for the Tyr176X variant has not been established, but studies suggest that this variant is more common in the Finnish population.