Objective: Eyes absent 4 (EYA4) is the causative gene of autosomal dominant non-syndromic hereditary hearing loss, DFNA10. We aimed to identify a copy number variation of EYA4 in a non-syndromic sensory neural hearing loss pedigree. Family and Clinical Evaluation: A Japanese family showing late-onset and progressive hearing loss was evaluated. A pattern of autosomal dominant inheritance of hearing loss was recognized in the pedigree. No cardiac disease was observed in any of the individuals. Methods: Targeted exon sequencing was performed using massively parallel DNA sequencing (MPS) analysis. Scanning of the array comparative genomic hybridization (aCGH) was completed and the copy number variation (CNV) data from the aCGH analysis was confirmed by matching all CNV calls with MPS analysis. Breakpoint detection was performed by whole-genome sequencing and direct sequencing. Sequencing results were examined, and co-segregation analysis of hearing loss was completed. Results: We identified a novel hemizygous indel that showed CNV in the EYA4 gene from the position 133,457,057 to 133,469,892 on chromosome 6 (build GRCh38/hg38) predicted as p.(Val124_Pro323del), and that was segregated with post-lingual and progressive autosomal dominant sensorineural hearing loss by aCGH analysis. Conclusion: Based on the theory of genotype-phenotype correlation with EYA4 mutations in terms of hearing loss and comorbid dilated cardiomyopathy, the region of amino acids 124 to 343 is hypothesized not to be the pathogenic region causing dilated cardiomyopathy. Additionally, the theory of genotype-phenotype correlation about the prevalence of dilated cardiomyopathy is thought to be rejected because of no correlation of deleted amino acid region with the prevalence of dilated cardiomyopathy. These results will help expand the research on both the coordination of cochlear transcriptional regulation and normal cardiac gene regulation via EYA4 transcripts and provide information on the genotype-phenotype correlations of DFNA10 hearing loss.
No abstract
Multiple bone disorders due to mutations in the human noggin (NOG) causes a variety of phenotypes. Hearing impairment due to stapes ankylosis secondary to bony degeneration is also a feature of these syndromes. We describe the case of an individual in a Japanese family with conductive hearing loss due to stapes ankylosis and hyperopia and dactylosymphysis. We revealed a novel NOG mutation, NM_005450.6:c.222 C > A / p.Tyr74*, and confirmed genetic significance.
Objective: Pneumococcal conjugate vaccines (PCVs) have been reported to reduce the incidence of myringotomy with tympanostomy tube insertion (MTTI) in children.However, little information is available focusing specific ages. We examined the prophylactic efficacy of PCVs on the onset of complex otitis media (ComOM) that requires MTTI.Method: From 2011, the public support for PCV7 started with the usual four-dose schedule and an emergency schedule for 2-to 4-year-old children in Japan. PCV7 was replaced with PCV13 in 2013. We reviewed the nationwide database obtained from the JMDC Claims Database (https://www.jmdc.co.jp/en/) to examine the MTTI incidence during the era before and after PCV introduction (from 2008 to 2010 and from 2011 to 2017, respectively). Subjects were analyzed by stratified age groups (from 0 to 8 years old) and in subdivided groups of 6 months (from 0 to 35 months old). We compared the MTTI incidence between the groups for each age as well as between those for each calendar year.Results: A significant reduction in the MTTI incidence was detected in the 1-year-old children of the PCV era compared to those of the pre-PCV era. The reduction rates were more prominent in the 12-17 months group as compared to the 18-23 months group (PCV7 p = .005 and PCV13 p = .011, PCV7 p = .014 and PCV13 p = .153, respectively). The significant difference in the 1-year-old children continued in six of seven calendar years from 2011 to 2017, whereas no significant reduction was detected in children >3 years old. Conclusions:The introduction of both PCV7 and PCV13 reduced MTTI incidences in children around 1 year old, and the effects were more prominent during the early half-periods. Our results support etiological evidence that pneumococcal infection in children aged 1 year and younger might play roles in the pathogenesis of ComOM that requires MTTI.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.