Abstract
ObjectiveThe aim of this study was to evaluate the GoldenGate microarray as a diagnostic tool and to elucidate the contribution of the genes on this array to the development of both nonsyndromic and syndromic sensorineural hearing loss in China.MethodsWe developed a microarray to detect 240 mutations underlying syndromic and nonsyndromic sensorineural hearing loss. The microarray was then used for analysis of 382 patients with nonsyndromic sensorineural hearing loss (including 15 patients with enlarged vestibular aqueduct syndrome), 21 patients with Waardenburg syndrome, and 60 unrelated controls. Subsequently, we analyzed the sensitivity, specificity, and reproducibility of this new approach after Sanger sequencing-based verification, and also determined the contribution of the genes on this array to the development of distinct hearing disorders.ResultsThe sensitivity and specificity of the microarray chip were 98.73% and 98.34%, respectively. Genetic defects were identified in 61.26% of the patients with nonsyndromic sensorineural hearing loss, and 9 causative genes were identified. The molecular etiology was confirmed in 19.05% and 46.67% of the patients with Waardenburg syndrome and enlarged vestibular aqueduct syndrome, respectively.ConclusionOur new mutation-based microarray comprises an accurate and comprehensive genetic tool for the detection of sensorineural hearing loss. This microarray-based detection method could serve as a first-pass screening (before next-generation-sequencing screening) for deafness-causing mutations in China.
Highlights
Hearing loss is the most common sensory-nerve disease worldwide [1], with approximately 250 million people suffering from moderate to severe hearing loss [2]
Genetic defects were identified in 61.26% of the patients with nonsyndromic sensorineural hearing loss, and 9 causative genes were identified
Approximately 30,000 babies are born with congenital hearing impairment annually in China [4], and nearly half of the cases of congenital deafness are estimated to be associated with genetic factors [5]
Summary
Hearing loss is the most common sensory-nerve disease worldwide [1], with approximately 250 million people suffering from moderate to severe hearing loss [2]. Approximately 30,000 babies are born with congenital hearing impairment annually in China [4], and nearly half of the cases of congenital deafness are estimated to be associated with genetic factors [5]. Roughly 70% of the cases are nonsyndromic [6] and, as of August 2015, >80 pathogenic nuclear genes associated with this disorder have been cloned. Beyond the mutations in these 4 genes, it is unclear which genetic defects are the most prevalent among SNHL patients in China To address this gap in our knowledge and to develop a microarray that is more comprehensive than the ones used to date, we selected key mutations from a larger number of deafness genes than were previously analyzed; these mutations were selected based on the prevalence at which they are reported in the literature
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