[Phenotype and genotype analysis of recessive hereditary moderate sensorineural hearing loss caused by new mutations in OTOGL gene].

Objective: To perform the phenotype and genetic analysis on two families with moderate sensorineural hearing impairment and determine the cause of deafness. Methods: The phenotype and genetic analysis was performed on the two hearing impairment pedigrees coming to Chinese PLA General Hospital from January 2014 to August 2020. DNA samples of the proband from family 1 and the parents from family 2 were collected and tested through next generation sequencing on all deafness genes, and Sanger sequencing was performed to verify the mutation sites. The reported pathogenic variants of the otogelin-like (OTOGL) gene, the autosomal recessive inherited deafness genes that cause moderate sensorineural hearing loss and the clinical manifestations of the deafness genes that have the similar expression location as the OTOGL gene were summarized and analyzed. Results: The pathogenic variants in the families were compound heterozygous variants in the OTOGL gene c.2773C>T/c.2826C>G (p.Arg925*/p.Tyr942*) and c.4455G>A/c.875C>G (Trp1485*/p.Ser292*), respectively. c.2773C>T was an already reported pathogenic variant causing hearing impairment in the literature, while c.2826C>G, c.4455G>A and c.875C>G were novel reported variant sites. The above four variants were classified as pathogenic variants according to the variant interpretation standards and guideline of the Amercian College of Medical Genetics and Genomics. Conclusions: Pathogenic variants in OTOGL gene is an important genetic factor leading to moderate sensorineural hearing loss. The newly discovered variant sites c.2826C>G, c.4455G>A and c.875C>G enrich the variant spectrum of OTOGL gene. The results of the current study provide a basis for genetic counseling of the related families and a new target for the treatment of hereditary hearing loss in the future.

[The application of extended high frequency audiometry in detecting the early hearing loss for polycystic ovarian syndrome].

Objective:To preliminarily explore the clinical significance of extended high frequency audiometry in evaluating the early hearing loss in patients with polycystic ovarian syndrome（PCOS）. The results were statistically analyzed. Method:The hearing threshold of forty young women diagnosed as PCOS and 20 healthy controls were obtained by using conventional audiometry（0.25-8.00 kHz） and extended high frequency（10-20 kHz） pure tone audiometry. Result:The hearing thresholds of the two groups were similar at conventional frequencies of 0.25，0.50，1.00，2.00 and 4.00 kHz（P>0.05）. The hearing threshold of PCOS group at 8-20 kHz frequency was significantly higher than that of the control group, and the difference was statistically significant（P<0.05）. The expanded high-frequency detectable rate was lower in PCOS group than that in control group, especially at 16 and 18 kHz （P<0.05） and the differences were statistically significant. Conclusion:The early hearing impairment of PCOS patients starts from the extended high frequency, which is more sensitive than the conventional pure tone audiometry in the early hearing impairment assessment of PCOS patients.

[Analysis of deafness-related gene mutations in 23 nonsyndromic hearing impairment families in Guangxi Zhuang Autonomous Region].

Objective:To investigate the genetic characteristics of the mutations responsible for nonsyndromic hearing loss in Guangxi Zhuang Autonomous Region, and analyze the deafness-related gene mutations in nonsyndromic hearing impairment families in this region.Method:In 23 nonsyndromic hearing impairment families,66 patients or their families were enrolled as family history group and 167 patients or their families without family histiory as control group, respectively. Deafness gene mutations were determined with deafness-related gene mutations detection kits. The mutation rates among the deafness probands, the hearing impairment patients and their audibility relatives were analyzied. Whole length sequences of the deafness-related gene were detected if there was mutation by the kits, to explore Guangxi region-specific mutation-sites.Result:Common deafness-related gene mutation rate in family history group(31.82%) was higher than that in control group(11.38%), including those that in GJB2 homozygous(21.21%), SLC26A4 homozygous (9.09%), both were higher than the control group (GJB2 homozygous 5.99%, SLC26A4 homozygous 3.59%) . The rate of common deafness-related gene mutations in the deafness probands was 34.78%, in the hearing impairment patients was 30.56%, in their audibility relatives was 29.63%, all of which were higher than those in the control group. We found three rarely seen mutations, SLC26A4 IVS11+47T>C, 1548insC and GJB2 109 A>G, by detecting the whole-length sequences of the deafness-related gene.Conclusion:The results indicated that GJB2 and SLC26A4 were the most frequent mutant genes in Guangxi region. Analysis of the individual family were helpful to linkage the mutations and the deafness.

[Analysis of the SLC26A4 mutation from 230 deafness patients in Guangxi region].

Objective:To investigate the mutation characteristics of SLC26A4 gene from 230 hearing loss patients in Guangxi region.Method:Two hundred thirty patients with hearing loss were enrolled in the study. Eight mutation sites in SLC26A4 gene were tested; the types of gene mutation and the inner ear CT features of the mutationpositive patients were analyzed.Result:Among 230 deafness patients,the total mutation rate of SLC26A4 gene is 2.61%(6/230). The types of gene mutation include SLC26A4 IVS7-2A> G heterozygous in 2 case(0.87%).1226G> A homozygous in 1 cases(0.43%),IVS7-2A>G，IVS11+47T>C and 1548insC mutations in 2 cases(0.87%).Conclusion:The mutation rate of SLC26A4 gene in Guangxi region is lower than the national average level. The main mutation type in Guangxi region is SLC26A4 IVS7 2A>G. In this study, two gene mutations (SLC26A4 IVS11+47T> C and 1548insC) are firstly found, suggesting that some rare mutation types of SLC26A4 may exist in patients living in Guangxi region.