The authors have no conflict of interest.
Article first published online: 3 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 1, pages 145–152, January 2013
How to Cite
Schrauwen, I., Sommen, M., Corneveaux, J. J., Reiman, R. A., Hackett, N. J., Claes, C., Claes, K., Bitner-Glindzicz, M., Coucke, P., Van Camp, G. and Huentelman, M. J. (2013), A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing. Am. J. Med. Genet., 161: 145–152. doi: 10.1002/ajmg.a.35737
Guy Van Camp and Matthew J. Huentelman contributed equally to this study.
How to cite this article: Schrauwen I, Sommen M, Corneveaux JJ, Reiman RA, Hackett NJ, Claes C, Claes K, Bitner-Glindzicz M, Coucke P, Van Camp G, Huentelman MJ. 2012. A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing. Am J Med Genet Part A 161A:145–152.
- Issue published online: 22 DEC 2012
- Article first published online: 3 DEC 2012
- Manuscript Accepted: 2 OCT 2012
- Manuscript Received: 15 MAY 2012
- Action on Hearing Loss. Grant Number: G45
- Great Ormond Street Hospital Children's Charity
- hearing loss;
- microdroplet PCR;
Implementing DNA diagnostics in clinical practice for extremely heterogeneous diseases such as hearing loss is challenging, especially when attempting to reach high sensitivity and specificity in a cost-effective fashion. Next generation sequencing has enabled the development of such a test, but the most commonly used genomic target enrichment methods such as hybridization-based capture suffer from restrictions. In this study, we have adopted a new flexible approach using microdroplet PCR-based technology for target enrichment, in combination with massive parallel sequencing to develop a DNA diagnostic test for autosomal recessive hereditary hearing loss. This approach enabled us to identify the genetic basis of hearing loss in 9 of 24 patients, a success rate of 37.5%. Our method also proved to have high sensitivity and specificity. Currently, routine molecular genetic diagnostic testing for deafness is in most cases only performed for the GJB2 gene and a positive result is typically only obtained in 10–20% of deaf children. Individuals with mutations in GJB2 had already been excluded in our selected set of 24 patients. Therefore, we anticipate that our deafness test may lead to a genetic diagnosis in roughly 50% of unscreened autosomal recessive deafness cases. We propose that this diagnostic testing approach represents a significant improvement in clinical practice as a standard diagnostic tool for children with hearing loss. © 2012 Wiley Periodicals, Inc.