RT Journal Article
SR Electronic
T1 Development of a genotyping microarray for Usher syndrome
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 153
OP 160
DO 10.1136/jmg.2006.044784
VO 44
IS 2
A1 Frans P M Cremers
A1 William J Kimberling
A1 Maigi Külm
A1 Arjan P de Brouwer
A1 Erwin van Wijk
A1 Heleen te Brinke
A1 Cor W R J Cremers
A1 Lies H Hoefsloot
A1 Sandro Banfi
A1 Francesca Simonelli
A1 Johannes C Fleischhauer
A1 Wolfgang Berger
A1 Phil M Kelley
A1 Elene Haralambous
A1 Maria Bitner-Glindzicz
A1 Andrew R Webster
A1 Zubin Saihan
A1 Elfride De Baere
A1 Bart P Leroy
A1 Giuliana Silvestri
A1 Gareth J McKay
A1 Robert K Koenekoop
A1 Jose M Millan
A1 Thomas Rosenberg
A1 Tarja Joensuu
A1 Eeva-Marja Sankila
A1 Dominique Weil
A1 Mike D Weston
A1 Bernd Wissinger
A1 Hannie Kremer
YR 2007
UL http://jmg.bmj.com/content/44/2/153.abstract
AB 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.