Sensorineural hearing loss is a common deficit and mainly occurs due to genetic factors. Recently, copy number variants (CNVs) in the STRC gene have also been recognized as a major cause of genetic hearing loss. We investigated the frequency of STRC deletions in the Japanese population and the characteristics of associated hearing loss. For CNV analysis, we employed a specialized method of Ion AmpliSeqTM sequencing, and confirmed the CNV results via custom array comparative genomic hybridization. We identified 17 probands with STRC homozygous deletions. The prevalence of STRC homozygous deletions was 1.7% in the hearing loss population overall, and 4.3% among mild-to-moderate hearing loss patients. A 2.63% carrier deletion rate was identified in both the hearing loss and the control population with normal hearing. In conclusion, our results show that STRC deletions are the second most common cause of mild-to-moderate hearing loss after the GJB2 gene, which accounts for the majority of genetic hearing loss. The phenotype of hearing loss is congenital and appears to be moderate, and is most likely to be stable without deterioration even after the age of 50. The present study highlights the importance of the STRC gene as a major cause of mild-to-moderate hearing loss.

A variant in a transcription factor gene, POU4F3, is responsible for autosomal dominant nonsyndromic hereditary hearing loss, DFNA15. To date, 14 variants, including a whole deletion of POU4F3, have been reported to cause HL in various ethnic groups. In the present study, genetic screening for POU4F3 variants was carried out for a large series of Japanese hearing loss (HL) patients to clarify the prevalence and clinical characteristics of DFNA15 in the Japanese population. Massively parallel DNA sequencing of 68 target candidate genes was utilized in 2,549 unrelated Japanese HL patients (probands) to identify genomic variations responsible for HL. The detailed clinical features in patients with POU4F3 variants were collected from medical charts and analyzed. Novel 12 POU4F3 likely pathogenic variants (six missense variants, three frameshift variants, and three nonsense variants) were successfully identified in 15 probands (2.5%) among 602 families exhibiting autosomal dominant HL, whereas no variants were detected in the other 1,947 probands with autosomal recessive or inheritance pattern unknown HL. To obtain the audiovestibular configuration of the patients harboring POU4F3 variants, we collected audiograms and vestibular symptoms of the probands and their affected family members. Audiovestibular phenotypes in a total of 24 individuals from the 15 families possessing variants were characterized by progressive HL, with a large variation in the onset age and severity with or without vestibular symptoms observed. Pure-tone audiograms indicated the most prevalent configuration as mid-frequency HL type followed by high-frequency HL type, with asymmetry observed in approximately 20% of affected individuals. Analysis of the relationship between age and pure-tone average suggested that individuals with truncating variants showed earlier onset and slower progression of HL than did those with non-truncating variants. The present study showed that variants in POU4F3 were a common cause of autosomal dominant HL.

The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF -related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD.

Background: Childhood obstructive sleep apnea (OSA) has important implications for growth, learning, behavior, cognition and cardiovascular health as well as snoring and OSA in adulthood. In this study, we elucidated the sex differences in polysomnographic (PSG) findings and pharyngeal radiographic data in pediatric OSA patients.Methods: Sixty three children (age between 3 and 15 years old) with OSA [defined as apnea-hypopnea index (AHI) ≥1/h by polysomnography] were enrolled. Lateral neck radiographs were obtained from the patients. All subjects were separated by age: pre-adolescent group (3-8 years old) and adolescent group (9-15 years old).Results: Overall, 45 patients in the pre-adolescent group (33 boys and 12 girls) and 18 patients in the adolescent group (10 boys and 8 girls) were enrolled, and sex differences were compared in each group. We found sex differences in craniofacial features and severity of OSA in the adolescent group, in which girls with OSA had more upper airway space, in addition to lower AHI, lower 3% oxygen desaturation index (ODI), higher minimum SO 2 and better sleep efficiency than the boys.Conclusions: The present study found revealed sex differences in pediatric OSA patients in the adolescent group. Girls in the adolescent group had more upper airway space in addition to lower AHI, lower 3% ODI, higher minimum SO 2 and better sleep efficiency than boys.

Polyamines are essential for biofilm formation in Escherichia coli, but it is still unclear which polyamines are primarily responsible for this phenomenon. To address this issue, we constructed a series of E. coli K-12 strains with mutations in genes required for the synthesis and metabolism of polyamines. Disruption of the spermidine synthase gene (speE) caused a severe defect in biofilm formation. This defect was rescued by the addition of spermidine to the medium, but not by putrescine or cadaverine. A multidrug/spermidine efflux pump membrane subunit (MdtJ)-deficient strain was anticipated to accumulate more spermidine and result in enhanced biofilm formation than the MdtJ+ strain. However, the mdtJ mutation did not affect intracellular spermidine or biofilm concentrations. E. coli has the spermidine acetyltransferase (SpeG) and glutathionylspermidine synthetase/amidase (Gss) to metabolize intracellular spermidine. Under the biofilm-forming condition, not Gss but SpeG plays a major role in decreasing the too high intracellular spermidine concentrations. Additionally, PotFGHI can function as a compensatory importer of spermidine when PotABCD is absent under the biofilm-forming condition. Lastly, we reported here that, in addition to intracellular spermidine, the periplasmic binding protein (PotD) of the spermidine preferential ABC transporter is essential for stimulating biofilm formation. IMPORTANCE Previous reports have speculated on the effect of polyamines on bacterial biofilm formation. However, the regulation of biofilm formation by polyamines in Escherichia coli has not yet been assessed. The identification of polyamines that stimulate biofilm formation is important for developing novel therapies for biofilm-forming pathogens. This study sheds light on biofilm regulation in E. coli. Our findings provide conclusive evidence that only spermidine can stimulate biofilm formation in E. coli cells, but not putrescine and cadaverine. Lastly, ΔpotD inhibits biofilm formation even though the spermidine is synthesized inside the cells from putrescine. Since PotD is significant for biofilm formation and there is no ortholog of PotABCD transporter in humans, PotD could be a target for the development of biofilm inhibitors.

Background: Childhood obstructive sleep apnea (OSA) has important implications for growth, learning, behavior, cognition and cardiovascular health as well as snoring and OSA in adulthood. In this study, we elucidated the sex differences in polysomnographic (PSG) findings and pharyngeal radiographic data in pediatric OSA patients. Methods: Sixty three children (age between 3 and 15 years old) with OSA [defined as apnea-hypopnea index (AHI) ≥1/h by polysomnography] were enrolled. Lateral neck radiographs were obtained from the patients. All subjects were separated by age: pre-adolescent group (3-8 years old) and adolescent group (9-15 years old). Results: Overall, 45 patients in the pre-adolescent group (33 boys and 12 girls) and 18 patients in the adolescent group (10 boys and 8 girls) were enrolled, and sex differences were compared in each group. We found sex differences in craniofacial features and severity of OSA in the adolescent group, in which girls with OSA had more upper airway space, in addition to lower AHI, lower 3% oxygen desaturation index (ODI), higher minimum SO 2 and better sleep efficiency than the boys. Conclusions: The present study found revealed sex differences in pediatric OSA patients in the adolescent group. Girls in the adolescent group had more upper airway space in addition to lower AHI, lower 3% ODI, higher minimum SO 2 and better sleep efficiency than boys.

No abstract

No abstract