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. 2012;7(2):e31276.
doi: 10.1371/journal.pone.0031276. Epub 2012 Feb 24.

Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study

Shin-ichi Usami  1 , Shin-ya Nishio, Makoto Nagano, Satoko Abe, Toshikazu Yamaguchi; Deafness Gene Study Consortium
Collaborators, Affiliations

Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study

Shin-ichi Usami et al. PLoS One. 2012.

Abstract

Although etiological studies have shown genetic disorders to be a common cause of congenital/early-onset sensorineural hearing loss, there have been no detailed multicenter studies based on genetic testing. In the present report, 264 Japanese patients with bilateral sensorineural hearing loss from 33 ENT departments nationwide participated. For these patients, we first applied the Invader assay for screening 47 known mutations of 13 known deafness genes, followed by direct sequencing as necessary. A total of 78 (29.5%) subjects had at least one deafness gene mutation. Mutations were more frequently found in the patients with congenital or early-onset hearing loss, i.e., in those with an awareness age of 0-6 years, mutations were significantly higher (41.8%) than in patients with an older age of awareness (16.0%). Among the 13 genes, mutations in GJB2 and SLC26A4 were mainly found in congenital or early-onset patients, in contrast with mitochondrial mutations (12S rRNA m.1555A>G, tRNA(Leu(UUR)) m.3243A>G), which were predominantly found in older-onset patients. The present method of simultaneous screening of multiple deafness mutations by Invader assay followed by direct sequencing will enable us to detect deafness mutations in an efficient and practical manner for clinical use.

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Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts. The authors did not receive funding from the Department of Clinical Genomics, Biomedical Laboratories, Inc. They felt that for genetic analysis of patients with hearing impairment in which many gene/gene mutations are involved, Invader Assay is the appropriate choice. However, for patent reasons, the authors cannot develop this method independently. The development of this method was therefore performed in collaboration with Biomedical Laboratories. This relationship had no influence on results and the direct sequencing results were all double checked for accuracy. Although Invader Assay is more efficient, if a method other than Invader Assay had been used, the results would have been identical.

Figures

Figure 1
Figure 1. Detection rate by onset/awareness age and severity of hearing loss.
Diagnostic rates and detection rates of this simultaneous multiple mutations screening and direct sequencing for biallelic mutations in autosominal recessive genes or mitochondrial mutations increased when restricted to congenital/early-onset hearing loss, and moderate or severe hearing loss. Combined direct sequence and invader screening enhanced the diagnostic rate but not the mutation detection rate.
Figure 2
Figure 2. Radiographic findings and detection rate.
Detection rate was elevated when subjects were restricted to those with inner ear anomaly or EVA. Combined direct sequence and invader screening enhanced the diagnostic rate but not the mutation detection rate.
See this image and copyright information in PMC

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