TY - JOUR T1 - Development of a genotyping microarray for Usher syndrome JF - Journal of Medical Genetics JO - J Med Genet SP - 153 LP - 160 DO - 10.1136/jmg.2006.044784 VL - 44 IS - 2 AU - Frans P M Cremers AU - William J Kimberling AU - Maigi Külm AU - Arjan P de Brouwer AU - Erwin van Wijk AU - Heleen te Brinke AU - Cor W R J Cremers AU - Lies H Hoefsloot AU - Sandro Banfi AU - Francesca Simonelli AU - Johannes C Fleischhauer AU - Wolfgang Berger AU - Phil M Kelley AU - Elene Haralambous AU - Maria Bitner-Glindzicz AU - Andrew R Webster AU - Zubin Saihan AU - Elfride De Baere AU - Bart P Leroy AU - Giuliana Silvestri AU - Gareth J McKay AU - Robert K Koenekoop AU - Jose M Millan AU - Thomas Rosenberg AU - Tarja Joensuu AU - Eeva-Marja Sankila AU - Dominique Weil AU - Mike D Weston AU - Bernd Wissinger AU - Hannie Kremer Y1 - 2007/02/01 UR - http://jmg.bmj.com/content/44/2/153.abstract N2 - Background: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. Methods: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. Results: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. Conclusion: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool. ER -