MARVELD2 (DFNB49) Mutations in the Hearing Impaired Central European Roma Population - Prevalence,Clinical Impact and the Common Origin

Background

In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies.

Methods

We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C.

Results

One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss.

Conclusions

We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.     

Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss

BACKGROUND:

Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non-syndromic recessive hearing loss DFNB29.

AIM:

We describe a Moroccan SF7 family with non-syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness.

MATERIALS AND METHODS:

Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene.

RESULTS:

Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4.

CONCLUSION:

These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.     

Absence of mutations in GJB2 (Connexin-26) gene in an ethnic group of southwest Iran

BACKGROUND:

The common GJB2 gene mutation (35delG) has been previously reported from Iranian patients that were affected with nonsyndromic autosomal recessive deafness. We, therefore, for the first time, investigated the prevalence and frequency of the GJB2 gene mutation in the Iranian deaf population with Arabian origins.

MATERIALS AND METHODs:

We amplified and sequenced the entire coding sequence of the GJB2 gene from 61 deaf patients and 26 control subjects.

RESULT:

None of the analyzed samples revealed deafness-associated mutation.

CONCLUSION:

This finding differs from several reports from Iran as we have focused on the GJB2 gene that possesses various mutations as the cause of congenital recessive deafness.     

Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment

Background

Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population.

Methods

A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT.

Results

None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18% of the Tibetan patients and 21.67% of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33% of the Han patients. Common molecular etiologies, GJB2 and SLC26A4 mutations, were rare in the Tibetan Chinese deaf population.

Conclusion

The mutation spectrum of hearing loss differs significantly between Chinese Tibetan patients and Han patients. The incidence of inner ear malformation in Tibetans is almost as high as that in Han deaf patients, but the types of malformation vary greatly. Hypoxia and special environment in plateau may be one cause of developmental inner ear deformity in this population.     

Long-Term Cochlear Implant Outcomes in Children with GJB2 and SLC26A4 Mutations

Objectives

To investigate speech and language outcomes in children with cochlear implants (CIs) who had mutations in common deafness genes and to compare their performances with those without mutations.

Study Design

Prospective study.

Methods

Patients who received CIs before 18 years of age and had used CIs for more than 3 years were enrolled in this study. All patients underwent mutation screening of three common deafness genes: GJB2, SLC26A4 and the mitochondrial 12S rRNA gene. The outcomes with CIs were assessed at post-implant years 3 and 5 using the Categories of Auditory Performance (CAP) scale, Speech Intelligibility Rating (SIR) scale, speech perception tests and language skill tests.

Results

Forty-eight patients were found to have confirmative mutations in GJB2 or SLC26A4, and 123 without detected mutations were ascertained for comparison. Among children who received CIs before 3.5 years of age, patients with GJB2 or SLC26A4 mutations showed significantly higher CAP/SIR scores than those without mutations at post-implant year 3 (p = 0.001 for CAP; p = 0.004 for SIR) and year 5 (p = 0.035 for CAP; p = 0.038 for SIR). By contrast, among children who received CIs after age 3.5, no significant differences were noted in post-implant outcomes between patients with and without mutations (all p > 0.05).

Conclusion

GJB2 and SLC26A4 mutations are associated with good post-implant outcomes. However, their effects on CI outcomes may be modulated by the age at implantation: the association between mutations and CI outcomes is observed in young recipients who received CIs before age 3.5 years but not in older recipients.     

Marital Structure,Genetic Fitness,and the <Emphasis Type="Italic">GJB2</Emphasis> Gene Mutations among Deaf People in Yakutia (Eastern Siberia,Russia)

Autosomal recessive deafness type 1A (DFNB1A) caused by mutations in the GJB2 gene (Cx26) is the main cause of nonsyndromic hearing impairment in many populations worldwide. It is considered that widespread prevalence of DFNB1A can be due to the long tradition of intermarriages between deaf people (assortative marriages) combined with their increased social adaptation and genetic fitness after widespread introduction of sign language. For the first time, the data on mating structure and reproduction of deaf people living in Yakutia (Eastern Siberia, Russia) are presented in comparison with contribution of the GJB2 gene mutations to the etiology of hearing impairment. The relative fertility of deaf people compared to their hearing siblings is 0.78 (mean number of children 1.76 ± 0.10 and 2.24 ± 0.09 to deaf and their hearing siblings, respectively, p = 0.0018). The rate of assortative marriages among deaf people is 77.1% (81 of 105 marriages). Biallelic mutations in the GJB2 gene were found in 42.2% (43 of 102) of examined deaf people, which corresponded to diagnosis DFNB1A for these patients. A comparison of deaf marital partners by GJB2 status revealed a proportion of noncomplementary marriages (24%) in which hearing loss in both partners was caused by the presence of biallelic GJB2 gene mutations resulting in the birth of only deaf children in such couples. Thus, the set of obtained data including a relatively high genetic fitness (expressed as relative fertility) of deaf people in Yakutia in combination with a high rate of assortative marriages among them and high incidence of DFNB1A indicates a possible weakening of selection against such trait as “deafness” and a possible increase in the frequency of GJB2 mutant alleles in subsequent generations.     

GJB2-associated hearing loss undetected by hearing screening of newborns

The hearing loss caused by GJB2 mutations is usually congenital in onset, moderate to profound in degree, and non-progressive. The objective of this study was to study genotype/phenotype correlations and to document 14 children with biallelic GJB2 mutations who passed newborn hearing screening (NHS). Genetic testing for GJB2 mutations by direct sequencing was performed on 924 individuals (810 families) with hearing loss, and 204 patients (175 families) were found to carry biallelic GJB2 mutations. NHS results were obtained through medical records. A total of 18 pathological mutations were identified, which were subclassified as eight inactivating and 10 non-inactivating mutations. p.I128M and p.H73Y were identified as novel missense GJB2 mutations. Of the 14 children with biallelic GJB2 mutations who passed NHS, eight were compound heterozygotes and 3 were homozygous for the c.235delC mutation in GJB2, and the other three combinations of non-c.235delC mutations identified were p.Y136X-p.G45E/p.V37I heterozygous, c.512ins4/p.R143W heterozygous, and p.V37I/p.R143W heterozygous. These 14 cases demonstrate that the current NHS does not identify all infants with biallelic GJB2 mutations. They suggest that the frequency of non-penetrance at birth is approximately 6.9% or higher in DFNB1 patients and provide further evidence that GJB2 hearing loss may not always be congenital in onset.     

Analysis of <Emphasis Type="Italic">GJB6</Emphasis> (Сx30) and <Emphasis Type="Italic">GJB3</Emphasis> (Сx31) genes in deaf patients with monoallelic mutations in <Emphasis Type="Italic">GJB2</Emphasis> (Сx26) gene in the Sakha Republic (Yakutia)

Тhe DNA testing of autosomal recessive deafness type 1A (DFNB1A, MIM 220290) is complicated when deaf patients have only monoallelic (heterozygous) recessive mutations in the GJB2 (Сх26) gene that is uninformative for establishment of diagnosis. Such patients may be “random” heterozygous carriers of GJB2 mutations as well as have the mutant allele in a cis-regulatory region of GJB2 gene, in element genes encoding other connexins: GJB6 (Сх30) or GJB3 (Сх31). Previous studies of genetic causes of hearing loss in patients from Yakutia were directed to search for only mutations in the GJB2 gene, and the DNA diagnostics was uninformative for 9.7% (38/393) of the patients with monoallelic GJB2 mutations. In this work the search for mutations in genes GJB3 and GJB6 and two deletions с.del(GJB6-D13S1830) and с.del(GJB6-D13S1854) to the cis-regulatory region of GJB2 gene was conducted in 35 patients with GJB2 monoallelic mutations and in 104 normal hearing individuals. The genes studied are two synonymous substitution c.489G>A (р.Leu163Leu) (GJB6) and c.357C>T (р.Asn119Asn) (GJB3) have been found, probably do not have clinical significance, and two nonsynonymous substitution c.301G>A (p.Glu101Lys) (GJB6) and с.580G>A (p.Ala194Thr) (GJB3). Additional experimental evidences are needed for confirmation of pathogenic significance of detected nonsynonymous substitutions in development of hearing loss in studied patients. Diagnosis of the DFNB1A was confirmed in only one patient, who was discovered by the deletion с.del(GJB6-D13S1830) (GJB2) in combination with a recessive mutation с.35delG (GJB2). In general, our results indicate low contribution of mutations in genes GJB6 and GJB3 in hearing loss etiology in Yakutia.     

Comparison of Various Anthropometric Indices as Risk Factors for Hearing Impairment in Asian Women

Background

The objective of the present study was to examine the associations between various anthropometric measures and metabolic syndrome and hearing impairment in Asian women.

Methods

We identified 11,755 women who underwent voluntary routine health checkups at Yeungnam University Hospital between June 2008 and April 2014. Among these patients, 2,485 participants were <40 years old, and 1,072 participants lacked information regarding their laboratory findings or hearing and were therefore excluded. In total 8,198 participants were recruited into our study.

Results

The AUROC value for metabolic syndrome was 0.790 for the waist to hip ratio (WHR). The cutoff value was 0.939. The sensitivity and specificity for predicting metabolic syndrome were 72.7% and 71.7%, respectively. The AUROC value for hearing loss was 0.758 for WHR. The cutoff value was 0.932. The sensitivity and specificity for predicting hearing loss were 65.8% and 73.4%, respectively. The WHR had the highest AUC and was the best predictor of metabolic syndrome and hearing loss. Univariate and multivariate linear regression analyses showed that WHR levels were positively associated with four hearing thresholds including averaged hearing threshold and low, middle, and high frequency thresholds. In addition, multivariate logistic analysis revealed that those with a high WHR had a 1.347–fold increased risk of hearing loss compared with the participants with a low WHR.

Conclusion

Our results demonstrated that WHR may be a surrogate marker for predicting the risk of hearing loss resulting from metabolic syndrome.     

The prevalence of connexin 26 ( GJB2) mutations in the Chinese population

Mutations in GJB2, encoding gap junction beta 2 protein (connexin 26), are responsible for the commonest form of non-syndromic recessive deafness in many populations. It has been reported recently that the most common 35delG mutation in GJB2 is exceptionally low in Japanese and Korean populations, but another deletion, 235delC, is relatively frequent. Since the Chinese constitute approximately one fifth of the global population, the frequency of GJB2 mutations in the population has important implications for understanding worldwide causes of genetic deafness. To determine whether GJB2 mutations are an important cause of deafness in Chinese, we conducted mutation screening for GJB2 in 118 deaf Chinese probands, including 60 from simplex and 58 from multiplex families with non-syndromic deafness, and 150 normal hearing Chinese controls. Four mutations, including 235delC, 299-300delAT, V37I, and 35delG, were found in the patients. Thirty-nine percent of the probands had a GJB2mutation. Of the 118 probands, 19 carried two definitely pathogenic mutations: three among the 58 multiplex cases (5.2%) and 16 among the 60 simplex cases (26.7%). Twenty-seven probands (22.9%) were found to carry only single GJB2 mutations. None of them had mutations in exon 1 of GJB2 and or the 342-kb deletion of GJB6. The 235delC mutation was the most prevalent mutation (20.3% of alleles), accounting for 81% of the pathologic alleles in multiplex cases and 67% in simplex cases. Analysis of the affected haplotypes in the patients with the homozygous 235delC mutation yielded evidence for a single origin of the mutation. The carrier frequency of the 235delC mutation in control subjects with normal hearing was 1.3%. The 35delG mutation was only noted as a heterozygous change in two simplex cases (1.2% of alleles). These results indicated that mutations in GJB2 are a major cause of inherited and sporadic congenital deafness in the Chinese population. The 235delC mutation, rather than 35delG, is the most common mutation found in the Chinese deaf population. Our data support the view that specific combinations of GJB2 mutation exist in different populations.     

Occupational Hearing Loss among Chinese Municipal Solid Waste Landfill Workers: A Cross-Sectional Study

Background

Occupational hearing loss is an increasingly prevalent occupational condition worldwide, and has been reported to occur in a wide range of workplaces; however, its prevalence among workers from municipal solid waste landfills (MSWLs) remains less clear. This study aimed to investigate the occupational hearing loss among Chinese MSWL workers.

Methods

A cross-sectional study of 247 workers from 4 Chinese MSWLs was conducted. Noise and total volatile organic compounds (TVOCs) levels at worksites were determined. We conducted hearing examinations to determine hearing thresholds. A worker was identified as having hearing loss if the mean threshold at 2000, 3000 and 4000 Hz in either ear was equal to or greater than 25 dB. Prevalence of occupational hearing loss was then evaluated. Using unconditional Logistic regression models, we estimated the odds ratios (ORs) of MSWL work associated with hearing loss.

Results

According to the job title for each worker, the study subjects were divided into 3 groups, including group 1 of 63 workers without MSWL occupational hazards exposure (control group), group 2 of 84 workers with a few or short-period MSWL occupational hazards exposure, and group 3 of 100 workers with continuous MSWL occupational hazards exposure. Both noise and TVOCs levels were significantly higher at worksites for group 3. Significantly poorer hearing thresholds at frequencies of 2000, 3000 and 4000 Hz were found in group 3, compared with that in group 1 and group 2. The overall prevalence rate of hearing loss was 23. 5%, with the highest in group 3 (36.0%). The OR of MSWL work associated with hearing loss was 3.39 (95% confidence interval [CI]: 1.28-8.96).

Conclusion

The results of this study suggest significantly higher prevalence of hearing loss among MSWL workers. Further studies are needed to explore possible exposure-response relationship between MSWL occupational hazards exposure and hearing loss.     

人工耳蜗植入聋儿术前基因检测及家系分析

摘要: 国内外研究表明GJB2、SLC26A4(PDS)和线粒体DNA(Mitochondrial DNA, mtDNA)的病理性突变导致了大部分的遗传性聋。 文章收集了2006年4月~2007年9月接受人工耳蜗(Cochlear implant, CI)植入的14 例患儿及其父母的外周血, 应用基因诊断方法进行 GJB2、SLC26A4(PDS)和mtDNA 1555位点突变检测。结果显示, 35.7%的患儿检测到致病突变, 其中28.6%为GJB2基因突变, 类型均为235delC纯和突变, 其父母为携带GJB2 235delC的杂和子; 7.1%为mtDNA A1555G突变, 其母亲亦携带mtDNA A1555G突变。这表明CI 植入聋儿最常见的基因突变是GJB2 235delC突变, 其次是mtDNA A1555G突变, 通过对耳聋家系常见致病基因的检测和家系分析, 可以对优生优育及减少耳聋发病率提供科学准确的遗传信息。     

Age- and Gender-Related Mean Hearing Threshold in a Highly-Screened Population: The Korean National Health and Nutrition Examination Survey 2010–2012

Background

In evaluating hearing disability in medicolegal work, the apportionment of age- and gender-related sensorineural hearing loss should be considered as a prior factor, especially for the elderly. However, in the literature written in the English language no studies have reported on the age- and gender-related mean hearing threshold for the South Korean population.

Objective

This study aimed to identify the mean hearing thresholds in the South Korean population to establish reference data and to identify the age- and gender-related characteristics.

Methods

This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government, the data of which was disclosed to the public. A total of 15,606 participants (unweighted) representing 33,011,778 Koreans (weighted) with normal tympanic membrane and no history of regular or occupational noise exposure were selected and analyzed in this study. The relationship between the hearing threshold level and frequency, age, and gender was investigated and analyzed in a highly-screened population by considering the sample weights of a complex survey design.

Results

A gender ratio difference was found between the unweighted and the weighted designs: male:female, 41.0%: 59.0% (unweighted, participants) vs. 47.2%:52.8% (weighted, representing population). As age increased, the hearing threshold increased for all frequencies. Hearing thresholds of 3 kHz, 4 kHz, and 6 kHz showed a statistical difference between both genders for people older than 30, with the 4 kHz frequency showing the largest difference. This paper presents details about the mean hearing threshold based on age and gender.

Conclusions

The data from KNHANES 2010–2012 showed gender differences at hearing thresholds of 3 kHz, 4 kHz, and 6 kHz in a highly-screened population. The most significant gender difference in relation to hearing threshold was observed at 4 kHz. The hearing thresholds at all of the tested frequencies worsened with increasing age. The mean hearing thresholds suggested in this study will be useful for the formulation of healthcare-related hearing policies and used as reference data for disability ratings for hearing loss due to various causes.     

Variants of OTOF and PJVK genes in Chinese patients with auditory neuropathy spectrum disorder

Background

Mutations in OTOF and PJVK genes cause DFNB9 and DFNB59 types of hearing loss, respectively. The patients carrying pathogenic mutations in either of these genes may show the typical phenotype of auditory neuropathy spectrum disorder (ANSD). The aim of the present study was to identify OTOF and PJVK mutations in sporadic ANSD patients.

Methods and Findings

A total of 76 unrelated Chinese non-syndromic ANSD patients were sequenced on the gene OTOF and PJVK exon by exon. Variants were valued in 105 controls with normal hearing to verify the carrying rate. We identified one pathogenic mutation (c.1194T>A) and three novel, possibly pathogenic, variants (c.3570+2T>C, c.4023+1 G>A, and c.1102G>A) in the OTOF gene, and one novel, possibly pathogenic, variant (c.548G>A) in PJVK. Moreover, we found three novel missense mutations within the exons of OTOF.

Conclusions

As we identified 4 and 1 possible pathogenic variants of the OTOF gene and the PJVK gene, respectively, we believe that screening in these genes are important in sporadic ANSD patients. The pathogenicity of these novel mutations needs further study because of their single heterozygous nature. Knowledge on the mutation spectra of these genes in Chinese would be beneficial in understanding the genetic character of this worldwide disease.     

The Association between Metabolic Syndrome or Chronic Kidney Disease and Hearing Thresholds in Koreans: The Korean National Health and Nutrition Examination Survey 2009-2012

Background

The aim of this study was to determine whether metabolic syndrome (MetS) or chronic kidney disease (CKD) is associated with hearing thresholds in the general Korean population.

Patients and Methods

A total of 16,554 participants were included in this study. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III guidelines, and CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m² or a dipstick proteinuria result of ≥1+. The hearing thresholds were measured at 0.5, 1, 2, 3, 4, and 6 kHz. Low-frequency (Freq) was defined as pure-tone averages at 0.5 and 1 kHz, while Mid-Freq and High-Freq were defined as the average thresholds at mid-frequency (2 and 3 kHz) and high frequency (4 and 6 kHz), respectively.

Results

In men, the hearing thresholds were 15.1 ± 14.5 dB, 22.2 ± 21.3 dB, and 37.3 ± 26.5 dB for Low-, Mid-, and High-Freq, respectively. In women, the hearing thresholds were 14.9 ± 15.3 dB, 16.6 ± 18.0 dB, and 26.1 ± 21.5 dB for Low-, Mid-, and High-Freq, respectively. The hearing thresholds for men were significantly higher than the hearing thresholds for women in all 3 threshold categories. Male and female subjects with MetS or CKD had higher hearing thresholds than the subjects that did not have these disorders. In the multivariate analysis, MetS was associated with increased hearing thresholds in women, and CKD was associated with increased hearing thresholds in men and women.

Conclusion

MetS is associated with hearing thresholds in women, and CKD is associated with hearing thresholds in men and women. Therefore, patients with MetS or CKD should be closely monitored for hearing impairment.     

Components of Metabolic Syndrome as Risk Factors for Hearing Threshold Shifts

Background

Hearing loss was a common, chronically disabling condition in the general population and had been associated with several inflammatory diseases. Metabolic syndrome, which was associated with insulin resistance and visceral obesity, was considered a chronic inflammatory disease. To date, few attempts had been made to establish a direct relationship between hearing loss and metabolic syndrome. The aim of the present study was to investigate the relationship between metabolic syndrome and hearing loss by analyzing the data in the reports of the National Health and Nutrition Examination Survey 1999–2004.

Methods

This study included 2100 participants aged ≤ 65 years who enrolled in the National Health and Nutrition Examination Survey (1999–2004). We examined the relationship between the presence of different features of metabolic syndrome in the participants and their pure-tone air-conduction hearing thresholds, including low-frequency and high-frequency thresholds.

Results

After adjusting for potential confounders, such as age, medical conditions, and smoking status, the participants with more components of metabolic syndrome were found to have higher hearing thresholds than those with fewer components of metabolic syndrome (p < 0.05 for a trend). The low-frequency hearing threshold was associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, elevated triglycerides, and a low level of high-density lipoprotein cholesterol (HDL-C) (p < 0.05 for all parameters).

Conclusions

The results indicated that the presence of a greater number of components of metabolic syndrome was significantly associated with the hearing threshold in the US adult population. Among the components of metabolic syndrome, the most apparent association was observed between low HDL and hearing loss.     

Linkage study of DFNB3 responsible for hearing loss in human

BACKGROUND:

Hearing disorders represent a significant health problem worldwide. Recessive inherited cases of the deafness are more prevalent in Pakistan due to consanguineous marriages. Deafness caused by DFNB3 is due to mutation in the gene MYO XVA and its prevalence among Pakistani population is about 5%.

MATERIALS AND METHODS:

Families with at least two or more individual affected with deafness were selected from different areas of District Okara of Pakistan. Six consanguineous families of different ethnic groups having deaf individuals were studied. All these families had three or more deaf individuals in either two or more sib ships. Family history was taken to minimize the chances of other abnormalities. Pedigrees drawn by using Cyrillic software (version 2.1) showed that all the marriages were consanguineous and the families have recessive mode of inheritance. Three STR markers were selected and amplified on all the samples of six families through PCR. The PCR products were then genotyped on non denaturing polyacrylamide gel electrophoresis (PAGE). Haplotypes were constructed to determine the pattern of inheritance and also to determine whether a family was linked or unlinked with known DFNB3 locus.

RESULTS:

One out of six families showed linkage to the DFNB3 while rest of the families remained unlinked. Carriers of deafness genes were identified and information was provided to the families on request.

CONCLUSION:

Knowledge about the genetic causes of deafness provide insight into the variable expression of genes involved in this hereditary problem and may allow the prediction and prevention of associated health problems.     

Effect of Cigarette Smoking and Passive Smoking on Hearing Impairment: Data from a Population–Based Study

Objectives

In the present study, we aimed to determine the effect of both active and passive smoking on the prevalence of the hearing impairment and the hearing thresholds in different age groups through the analysis of data collected from the Korea National Health and Nutrition Examination Survey (KNHANES).

Study Design

Cross-sectional epidemiological study.

Methods

The KNHANES is an ongoing population study that started in 1998. We included a total of 12,935 participants aged ≥19 years in the KNHANES, from 2010 to 2012, in the present study. Pure-tone audiometric (PTA) testing was conducted and the frequencies tested were 0.5, 1, 2, 3, 4, and 6 kHz. Smoking status was categorized into three groups; current smoking group, passive smoking group and non-smoking group.

Results

In the current smoking group, the prevalence of speech-frequency bilateral hearing impairment was increased in ages of 40−69, and the rate of high frequency bilateral hearing impairment was elevated in ages of 30−79. When we investigated the impact of smoking on hearing thresholds, we found that the current smoking group had significantly increased hearing thresholds compared to the passive smoking group and non-smoking groups, across all ages in both speech-relevant and high frequencies. The passive smoking group did not have an elevated prevalence of either speech-frequency bilateral hearing impairment or high frequency bilateral hearing impairment, except in ages of 40s. However, the passive smoking group had higher hearing thresholds than the non-smoking group in the 30s and 40s age groups.

Conclusion

Current smoking was associated with hearing impairment in both speech-relevant frequency and high frequency across all ages. However, except in the ages of 40s, passive smoking was not related to hearing impairment in either speech-relevant or high frequencies.     

GJB2 and mitochondrial A1555G gene mutations in nonsyndromic profound hearing loss and carrier frequencies in healthy individuals

This study aimed to assess mutations in GJB2 gene (connexin 26), as well as A1555G mitochondrial mutation in both the patients with profound genetic nonsyndromic hearing loss and healthy controls. Ninety-five patients with profound hearing loss (>90 dB) and 67 healthy controls were included. All patients had genetic nonsyndromic hearing loss. Molecular analyses were performed for connexin 26 (35delG, M34T, L90P, R184P, delE120, 167delT, 235delC and IVS1+1 A-->G) mutations, and for mitochondrial A1555G mutation. Twenty-two connexin 26 mutations were found in 14.7% of the patients, which were 35delG, R184P, del120E and IVS1+1 A-->G. Mitochondrial A1555G mutation was not encountered. The most common GJB2 gene mutation was 35delG, which was followed by del120E, IVS1+1 A-->G and R184P, and 14.3% of the patients segregated with DFNB1. In consanguineous marriages, the most common mutation was 35delG. The carrier frequency for 35delG mutation was 1.4% in the controls. 35delG and del120E populations, seems the most common connexin 26 mutations that cause genetic nonsyndromic hearing loss in this country. Nonsyndromic hearing loss mostly shows DFNB1 form of segregation.     

Investigation of the A1555G mutation in mitochondrial DNA (MT-RNR1) in groups of Brazilian individuals with nonsyndromic deafness and normal-hearing

BACKGROUND:

Mutations of mitochondrial DNA were described into two genes: The mitochondrially encoded 12S RNA (MT-RNR1) and the mitochondrially encoded tRNA serine^ucn (MT-TS1). The A1555G mutation in MT-RNR1 gene is a frequent cause of deafness in different countries.

AIM:

The aim of this work was to investigate the frequency of the A1555G mutation in the MT-RNR1 gene in the mitochondrial DNA in Brazilians individuals with nonsyndromic deafness, and listeners.

MATERIALS AND METHODS:

DNA samples were submitted to polymerase chain reaction and to posterior digestion with the Hae III enzyme.

RESULTS:

Seventy eight (78) DNA samples of deaf individuals were analyzed; 75 showed normality in the region investigated, two samples (2.5%) showed the T1291C substitution, which is not related to the cause of deafness, and one sample (1.3%) showed the A1555G mutation. Among the 70 non-impaired individuals no A1555G mutation or T1291C substitution was found.

CONCLUSION:

We can affirm that A1555G mutation is not prevalent, or it must be very rare in normal-hearing subjects in the State of Paraná, the south region of Brazil. The A1555G mutation frequency (1.3%) found in individual with nonsyndromic deafness is similar to those found in other populations, with nonsyndromic deafness. Consequently, it should be examined in deafness diagnosis. The investigation of the A1555G mutation can contribute towards the determination of the nonsyndromic deafness etiology, hence, contributing to the correct genetic counseling process.