Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss.

BACKGROUND: Low-frequency non-syndromic hearing loss (LFNSHL) is a rare form of hearing loss (HL). It is defined as HL at low frequencies (≤2,000 Hz) resulting in a characteristic ascending audiogram. LFNSHL is usually diagnosed postlingually and is progressive, leading to HL affecting other frequencies as well. Sometimes it occurs with tinnitus. Around half of the diagnosed prelingual HL cases have a genetic cause and it is usually inherited in an autosomal recessive mode. Postlingual HL caused by genetic changes generally has an autosomal dominant pattern of inheritance and its incidence remains unknown. SUMMARY: To date, only a handful of genes have been found as causing LFNSHL: well-established WFS1 and, reported in some cases, DIAPH1, MYO7A, TNC, and CCDC50 (respectively, responsible for DFNA6/14/38, DFNA1, DFNA11, DFNA56, and DFNA44). In this review, we set out audiological phenotypes, causative genetic changes, and molecular mechanisms leading to the development of LFNSHL. KEY MESSAGES: LFNSHL is most commonly caused by pathogenic variants in the WFS1 gene, but it is also important to consider changes in other HL genes, which may result in similar audiological phenotype.

The Genetic Background of Hearing Loss in Patients with EVA and Cochlear Malformation.

The most frequently observed congenital inner ear malformation is enlarged vestibular aqueduct (EVA). It is often accompanied with incomplete partition type 2 (IP2) of the cochlea and a dilated vestibule, which together constitute Mondini malformation. Pathogenic SLC26A4 variants are considered the major cause of inner ear malformation but the genetics still needs clarification. The aim of this study was to identify the cause of EVA in patients with hearing loss (HL). Genomic DNA was isolated from HL patients with radiologically confirmed bilateral EVA (n = 23) and analyzed by next generation sequencing using a custom HL gene panel encompassing 237 HL-related genes or a clinical exome. The presence and segregation of selected variants and the CEVA haplotype (in the 5' region of SLC26A4) was verified by Sanger sequencing. Minigene assay was used to evaluate the impact of novel synonymous variant on splicing. Genetic testing identified the cause of EVA in 17/23 individuals (74%). Two pathogenic variants in the SLC26A4 gene were identified as the cause of EVA in 8 of them (35%), and a CEVA haplotype was regarded as the cause of EVA in 6 of 7 patients (86%) who carried only one SLC26A4 genetic variant. In two individuals with a phenotype matching branchio-oto-renal (BOR) spectrum disorder, cochlear hypoplasia resulted from EYA1 pathogenic variants. In one patient, a novel variant in CHD7 was detected. Our study shows that SLC26A4, together with the CEVA haplotype, accounts for more than half of EVA cases. Syndromic forms of HL should also be considered in patients with EVA. We conclude that to better understand inner ear development and the pathogenesis of its malformations, there is a need to look for pathogenic variants in noncoding regions of known HL genes or to link them with novel candidate HL genes.

Relationship between abuse experience with suicidal ideation and behavior of junior middle school students in Chongqing / 中国学校卫生

Objective@#To explore the relationship between abuse experience with suicidal ideation and suicide attempts of junior middle school students, and to provide a reference for suicide prevention of junior middle school students.@*Methods@#Cluster sampling method were used to selct 10 289 junior middle school students from 25 districts and counties of Chongqing were included in the analysis of this study from July to September in 2020. And Questionnaire on Abuse in Childhood and Mental Health Scale for Middle School Students were applied to collect the data about demographic information, suicide ideation and behavior.@*Results@#The prevalence of suicidal ideation and suicide attempts among junior middle school students were 20.93% and 10.83%, respectively. Multivariate Logistic regression model found that after controlling for demographic variables and mental health, emotional abuse ( OR =2.07) and emotional neglect ( OR =2.03) showed higher correlations with suicidal ideation than the other three types of childhood abuse( OR physical neglect =1.19, OR physical abuse =1.60, OR sexual abuse =1.37, P <0.05); and sexual abuse ( OR =2.29) and physical neglect ( OR =1.87) showed higher associations with suicide attempt than the other three types of abuse( OR emotional abuse =1.63, OR emotional neglect =1.59, OR physical abuse =1.50, P <0.01).@*Conclusion@#All five types of child abuse were independent risk factors for suicidal ideation and suicide attempts, and emotional neglect and emotional abuse had a greater effect on suicidal ideation, sexual abuse and physical neglect had a greater effect on suicide attempts.