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Title
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A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing
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Author
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Abstract
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| 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 1020% 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. |
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Language
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English
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Source (journal)
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American journal of medical genetics : part A. - Bognor Regis, 2003, currens
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Publication
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Bognor Regis
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2013
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ISSN
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1552-4825
[print]
1552-4833
[online]
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DOI
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10.1002/AJMG.A.35737
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Volume/pages
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161A
:1
(2013)
, p. 145-152
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ISI
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000312939200023
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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