Usher syndrome (USH) is an autosomal recessive disorder comprising of bilateral sensorineural hearing loss, progressive loss of vision due to retinitis pigmentosa, and variable vestibular dysfunction. It is the most frequent cause of deafness and concurrent blindness with a prevalence of 1 in 16,000 to 1 in 50,000 in various populations. USH can be clinically classified by severity into three subtypes USH type III (USH III) is characterized by progressive, post-lingual hearing loss, variable onset and severity of retinitis pigmentosa, with or without vestibular dysfunction. Although the disorder is panethnic, and multiple causative genes have been identified, one mutation in the CLRN1 gene (p.N48K) has a carrier frequency of approximately 1 in 120 in the Ashkenazi Jewish population. Screening for one mutation will detect approximately 95% of carriers in this population. Carrier screening for USH III may be considered for individuals of Eastern European (Ashkenazi) Jewish ancestry before/during pregnancy.
Full gene sequencing is available for reproductive partners of known mutation carriers. Prenatal diagnosis is also available. Prior to ordering prenatal testing, please contact our laboratory at 212-241-7518 to discuss.
1. Adato A et al., (2002) USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. Eur J Hum Genet10:339?50.
2. Fields RR, et al., (2002) Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations. Am J Hum Genet71:607?17.
3. Joensuu T et al., (2001) Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet69:673?84.
4. Ness SL et al., (2003) Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher syndrome type III. J Med Genet. Oct40(10):767-72.
5. Petit C (2001) Usher syndrome: from genetics to pathogenesis. Annu Rev Genomics Hum Genet. 2:271-97.
6. Scott, S.A., Edelmann, L., Liu, L., Luo, M., Desnick, R.J. and Kornreich, R. Experience with carrier screening and prenatal diagnosis for sixteen Ashkenazi Jewish Genetic Diseases. Hum. Mutat. 31:1-11, 2010.
Amniotic Fluid: 10 ml in conical tube
Cultured Cells: two confluent T-25 flasks
Additionally, please send:
5-10 ml paternal blood in EDTA (lavender top) in case paternal confirmation studies are necessary
Forms and Brochures
Carrier Screening Requisition and Consent [PDF]
Expanded Ashkenazi Jewish Carrier Screening Brochure [PDF]
Ashkenazi Jewish Carrier Screening Panel