Acadian/French Canadian Usher Panel (216G>A in USH1C and 4338_4339delCT in USH2A) 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. There are two founder pathogenic variants in the Acadian/French Canadian population which cause Usher syndrome. This tests detects the two pathogenic variants that are common in this population which are the c.216G>A variant in the USH1C gene and the c.4338_4339delCT variant in the USH2A 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 1 is characterized by congenital, profound sensorineural hearing loss, vestibular dysfunction usually manifested as delayed walking (>18 months), and the onset of RP by the age of ten (Kimberling 2004). Usher Syndrome Type I is further subdivided into 6 types. Usher Syndrome Type 1C is due to pathogenic variants in the USH1C gene. It is thought that all incidences of Usher syndrome type 1C in the Acadian population are due a single variant (USH1C c.216G>A). Usher Syndrome Type 2 is characterized by a sloping congenital hearing loss that is mild to moderate in the low frequencies and severe to profound in the high frequencies. Vestibular problems are absent in Type 2, which distinguishes it from Type 1. RP is still present with an onset typically sometime in adolescence. Usher Type 2 is also further subdivided into three types with Usher Type 2A caused by pathogenic variants in the USH2A gene. A second founder mutation in the USH2A gene (USH2A c.4338_4339delCT) may account for up to 55% of all cases of Usher Type 2 cases in the Acadian/French Canadian population (Ebermann 2007, 2009).
These variants are all associated with autosomal recessive inheritance, meaning that an individual would need to inherit two pathogenic variants in order to have Usher syndrome. Two carriers have a 25% (or 1 in 4) chance of each passing on a pathogenic variant and having a child with Usher syndrome.Less
Individuals of Acadian/French Canadian decent who were born with hearing loss, of any severity, are candidates for the Acadian/French Canadian Hearing Loss Panel. This is true even if there is no family history of hearing loss, as this is the most common presentation. The Acadian/French Canadian Hearing Loss Panel 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 or Usher syndrome due to other variants with in these genes or other genes not covered by this test.
This test is performed by Sanger sequencing of the relevant exons and splice sites of the USH1C (exon 3) and USH2A (exon 20) genes. 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 each of the variants on this test varies. Variant specific carrier rates are listed below.
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