GJB2 Mutations Research Articles

Four novel connexin 32 mutations in X-linked Charcot–Marie–Tooth disease. Phenotypic variability and central nervous system involvement

Charcot–Marie–Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy–Lévy syndrome, and three of them were associated with mild clinical CNS manifestations.

Particular distribution of the GJB2/GJB6 gene mutations in Mexican population with hearing impairment

BackgroundHereditary sensorineural hearing loss (SNHL) is a genetically heterogeneous disorder worldwide. Mutations in the GJB2 gene are a frequent cause of hereditary SNHL. There is a prevalence of certain mutations in various populations which suggests that specific mutations may be influenced by ethnic background. ObjectiveTo analyze the prevalence of GJB2, GJB6 mutations in several geographic areas of Mexico in patients with hereditary SNHL. Materials and methodsOne hundred and forty Mexican unrelated propositi with prelingual SNHL were included in the study. All patients had three previous generations born in Mexico and belonged to no specific ethnic group. Analyses of the GJB2 and GJB6 genes and mt.1555A<G were performed in all subjects. ResultsTwenty-three homozygous mutations, 57 heterozygous mutations, 1 double heterozygous (GJB2/GJB6) and 59 wild-type genotypes in the GJB2 gene were observed. Three patients had the homozygous c.del35 mutation whereas 26 patients were heterozygous for this gene defect. Only one patient with the GJB6 gene deletion was present (it includes the double heterozygous GJB2/GJB6). The mt.1555A>G mutation was not detected. ConclusionWe found a great variety of mutations depending on the analyzed region in patients with SNHL; 57.86% of patients had affection in one or two alleles in GJB2 or GJB6 genes whereas 42.14% were wild-type. In some cases, allele distribution depended on region. Molecular studies of more genes involved in hereditary non-syndromic SNHL are required to completely confirm the molecular basis of hearing loss in Mexican population.

Is deafness etiology important for prediction of functional outcomes in pediatric cochlear implantation?

Conclusions: Implanted children with GJB2 mutations tended to achieve better functional outcomes than the two control groups, although clear-cut significance was not always achieved. Hearing loss etiology may be considered as one of the important predictors, but complex influence of other factors on postoperative performance should be included in cautious individual counseling. Objective: This study aimed to detect possible associations between hearing loss etiology and postoperative rehabilitation outcomes in prelingually deaf children, with a particular focus on hereditary deafness caused by connexin mutations. Methods: Eighty-one of 92 prelingually deaf implanted children, tested for DFNB1 mutations, were divided into 3 etiology groups and underwent audiological evaluation in tone audiometry, speech audiometry, monosyllabic words, and categories of auditory performance (CAP), conducted 1, 3, and 5 years after implantation. Results: Statistically significant differences (p < 0.05) for tone audiometry were obtained, particularly after the first and third year post implantation, between ‘connexin’ and ‘known’ etiology groups. In speech audiometry, the monosyllabic word test, and CAP, the connexin group of children scored significantly better than the two control groups only after 3 and 5 years. Although the rate of excellent performers was higher in the connexin group, poor results were achieved in all groups in similar proportion.

Update of the Spectrum ofGJB2Mutations in 107 Patients with Nonsyndromic Hearing Loss in the Fujian Population of China

Mutations in the GJB2 gene, encoding connexin26, which is expressed in the inner ear, have been shown to be responsible for the majority of nonsyndromic hearing loss (NSHL) cases. To update and evaluate the spectrum and prevalence of GJB2 mutations in the Fujian population, we screened exon 2 (coding), exon 1, and flanking introns of GJB2 in 107 NSHL probands and 61 individuals with normal hearing. Twelve different variants were identified, including three pathogenic mutations (c.235delC, c.299_300delAT, and c.508insAACG), one hypomorphic allele (p.V37I), three polymorphic variants (p.V27I, p.E114G, and p.I230T), and five rare variants (p.N62N, p.F115C, p.T123N, p.G21E, and p.F142I). The p.G21E and p.F142I variants were potentially pathogenic as predicted by PolyPhen-2, SIFT, and PROVEAN. The most common mutation was c.235delC with allele frequency 12.6% (27/214). The most common polymorphisms in the Fujian population were p.V27I and p.E114G, both detected at high frequency in probands and controls. The p.E114G variant was always in cis with p.V27I, and formed the haplotype, p.[V27I; E114G] in the Fujian population. Interestingly, only 17.76% (19/107) of NSHL probands had clearly defined pathogenic mutations in GJB2, indicating that the pathogenesis of NSHL in the Fujian population is heterogenous, and that further analysis of other NSHL genes is necessary.

A genotype–phenotype correlation in Sicilian patients with GJB2 biallelic mutations

The aim of this work was to study the genotype distribution of Sicilian patients with biallelic GJB2 mutations; to correlate genotype classes and/or specific mutations of GJB2 gene (35delG-non-35delG) with audiologic profiles. A total of 10 different mutations and 11 different genotypes were evidenced in 73 SNHL subjects; 35delG (90.36 % of cases) and IVS1+1 (13.69 %) were the most common mutations found in the cohort with a significant difference in the distribution between North and South Sicily. Audiological evaluation revealed a severe (16/73) to profound (47/73) hearing loss (HL) in 86.13 % of cases without significant difference between the degree of HL and the province of origin of the subjects (P = 0.727). The homozygous truncating (T/T) genotype was the most widespread (89.04 % of cases), with a severe-to-profound hearing impairment in 90.36 % of T/T class with respect to truncating/non-truncating (T/NT) and non-truncating/non-truncating (NT/NT) genotypes (P = 0.012). From the comparison of homozygous 35delG and 35delG/non-35delG genotypes, a more profound HL in the homozygous 35delG than in compound heterozygous 35delG/non-35delG (p < 0.0001) resulted. This study confirms that 35delG is the most common mutation in the Mediterranean area with a heterogeneous distribution of the genotypes between North and South Sicily; probands homozygotes for 35delG or presenting a T/T genotype are more apt to have a severe-to-profound HL.

Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum.

BackgroundRacial and regional factors are important for the clinical diagnosis of non-syndromic hearing impairment. Comprehensive genetic analysis of deaf patients in different regions of China must be performed to provide effective genetic counseling. To evaluate the mutational spectrum of south Chinese families, we performed genetic analysis for non-syndromic hearing impairment in this population.MethodsComplete clinical evaluations were performed on 701 unrelated patients with non-syndromic hearing impairment from six provinces in south China. Each subject was screened for common mutations, including SLC26A4 c.IVS7-2A > G, c.2168A > G; mitochondrial DNA m.1555A > G, m.1494C > T, m.7444G > A, m.7445A > G; GJB3 c.538C > T, c.547G > A; and WFS1 c.1901A > C, using pyrosequencing. GJB2 and SLC26A4 coding region mutation detection were performed using Sanger sequencing.ResultsGenetic analysis revealed that among the etiology of non-syndromic hearing impairment, GJB2, SLC26A4, and mitochondrial m.1555A > G mutations accounted for 18.0%, 13.1%, and 0.9%, respectively. Common mutations included GJB2 c.235delC, c.109G > A, SLC26A4 c.IVS7-2A > G, c.1229 T > C, and mitochondrial m.1555A > G. The total mutation rate was 45.1% in all patients examined in south China. Overall, the clear contribution of GJB2, SLC26A4, and mitochondrial m.1555A > G to the etiology of the non-syndromic deafness population in south China was 32.0%.ConclusionsOur study is the first genetic analysis of non-syndromic hearing impairment in south China, and revealed that a clear genetic etiology accounted for 32.0% of non-syndromic hearing cases in patients from these regions. The mutational spectrum of non-syndromic hearing impairment in the south Chinese population provides useful and targeted information to aid in genetic counseling.

WFS1 mutations in hearing-impaired children

Objective: Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic hearing impairment (HI). The objective of this study was to ascertain the presence of mutations in WFS1 among children with HI from unknown causes. Design: We screened 105 Finnish children with HI for mutations in exon 8 in WFS1. Study sample: Children were born in a defined area in Northern Finland and they had sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in mitochondrial DNA. Results: We found three rare variants and the novel p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel variant had arisen de novo. The p.Gly831Ser variant may be a new member to the group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of the rare variant p.Gly674Arg remained unclear. The other two rare variants, p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families. Conclusions: WFS1 gene mutations are a rare cause of HI among Finnish children with HI.

Mutation spectrum and genotype–phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: a large cohort study

Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype–phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype–phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype–phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

Spectrum of the GJB2 mutations in Belarussian patients with hearing loss. Findings of pilot genetic screening of hearing impairment in newborns

A total of 111 unrelated probands and their 8 sibs from Grodno oblast (Belarus) with bilateral isolated sensorineural hearing impairment were studied for the presence of mutations in the connexin 26 (GJB2) gene. Mutations were detected in 51 probands (46% of the sample). A significantly higher frequency of the GJB2 gene mutations was observed in familial cases of the disease with the autosomal recessive mode of inheritance (in 78% of families). Detected characteristics of the GJB2 gene mutation spectrum demonstrated that the using the algorithm, which was designed for Russian patients, is optimal for the molecular study of patients from Belarus. In the sample of patients with hearing loss, the highest (among other similar samples studied in the world) allele frequency of c.313_326del14 mutation (7% of all pathological GJB2 alleles) was registered; Polish origin of this deletion was suggested. It was demonstrated that detection of the GJB2 gene mutation on one patient’s chromosome only is insufficient to confirm a molecular genetic diagnosis of hearing loss of the DFNB1 genetic type (autosomal recessive hearing loss caused by the GJB2 gene mutations). Pilot screening for the GJB2 gene mutations in newborns from Grodno oblast was performed. The material from 235 children was studied during the screening; nine heterozygous carriers of the mutation were found. The c.35delG mutation was detected in a homozygous state in a single newborn (hearing loss of moderate severity was subsequently audiologically confirmed in this child).

Recurrent central nervous system white matter changes in charcot–Marie–Tooth type X disease

X-linked Charcot-Marie-Tooth (CMT1X) disease is caused by mutations in the GJB1 gene. We describe a young man who presented with recurrent central nervous symptoms and transient white matter changes in the setting of a novel mutation in the GJB1 gene. Evaluation included clinical examination, neuroimaging, electrophysiological, and molecular genetic studies. Clinical examination on 2 admissions 5 years apart demonstrated hemiparesis with findings of underlying peripheral neuropathy. Electrophysiologic studies revealed a sensorimotor polyneuropathy. MRI studies from both admissions revealed white matter changes, with improvement on an intervening study. Mutation analysis showed a novel mutation (c.98T>A; p.Ile33Asn) in the GJB1 gene. Mutations in GJB1 can result in recurrent central nervous system symptoms with transient white matter signal changes on MRI. In patients presenting with hemiparesis, the presence of signs of a peripheral neuropathy may facilitate identification of CMT1X, and is likely to affect clinical management.

Spectrum and frequency of GJB2 mutations causing deafness in the northwest of Iran

ObjectiveMutations in GJB2 and GJB6 which comprise DFNB1 locus cause up to half of all cases of the prelingual autosomal recessive non-syndromic hearing loss (ARNSHL) worldwide. This study has intended to assess the spectrum and frequency of GJB2/GJB6 mutations in northwest of Iran. Methods508 Patients with presumed ARNSHL were analyzed by applying ARMS-PCR, SSCP, PCR-RFLP and sequencing assays. ResultsSeventy-five (14.7%) different homozygous and eighty-seven (17.1%) different compound heterozygous genotypes were detected in this cohort. Concerning the GJB2 gene, c.35delG was the most prevalent mutation, accounting for 16.4% of the samples. In addition 29 sequence variations other than c.35delG mutation were distinguished in GJB2; namely, delE120, Ins A 290-291, R143Q, V37I, R32H, Y155X, V27I+T123N, F154F, 167delT, 312del14, 299-300delA, T8M, W24X, E114G+V27I, 235delC, R184P, V153I, S139N, A171T, M163V (unknown mutation), G127V, E147X, R127H, 35insG, R143W, V27I, G160S, E114G and IVS1+1G>A. Moreover, the IVS1+1G>A was accounted as a second common mutation. ConclusionsOverall, the frequency of GJB2 mutations (≥31%) is in agreement with other white population. These findings highlight the importance of the study of GJB2 gene in the diagnosis to provide early treatment and genetic counseling.

Clouston syndrome: gene diagnosis and pathogenic mechanism

Clouston syndrome,also named hidrotic ectodermal dysplasia,is an autosomal dominant genetic disease.It is characterized by hypotrichosis,nail dystrophy and palmoplantar hyperkeratosis.It is caused by mutations in the GJB6 gene.Up to date,there are four GJB6 missense mutations that can cause Clouston syndrome:G1 1R,A88V,V37E and D50N.This article reviews the progress of gene diagnosis and pathogenic mechanism of Clouston syndrome,which can contribute to etiological diagnosis,genetic counseling,intervention as well as treatment. Key words: Clouston syndrome; Gene GJB6; Connexin 30; Gene diagnosis; Pathogenic mechanism

Identification of both MT-RNR1 m.1555A>G and bi-allelic GJB2 mutations in probands with non-syndromic hearing loss

ObjectivesMutations in GJB2 and MT-RNR1 are common causes for non-syndromic sensorineural hearing loss (NSHL). In this study, we investigated the co-existence of both MT-RNR1 and bi-allelic GJB2 mutations in a large number of simplex and multiplex probands with NSHL. Methods485 simplex and 134 multiplex probands with NSHL were recruited for mutation screening of GJB2 and MT-RNR1 by bidirectional sequencing. Clinical features of probands with both MT-RNR1 and bi-allelic GJB2 mutations were further analyzed in comparison with extended family members. ResultsMT-RNR1m.1555A>G and bi-allelic GJB2 mutations were both detected in one (0.21%) simplex probands and two (1.49%) multiplex probands. Variable hearing phenotypes were found in a pair of siblings with both MT-RNR1 and bi-allelic GJB2 mutations. ConclusionMT-RNR1 and bi-allelic GJB2 mutations may co-exist not only in multiplex probands but also in simplex probands. The variable hearing phenotypes in closely-related family members may reflect the co-existence of different molecular causes and prompt extended genetic tests.

Analysis of CABP2 c.637+1g>t mutation in Iranian families with autosomal recessive non-syndromic hearing loss

BACKGROUND AND OBJECTIVE: Congenital hearing loss is the most common sensorineural defect in human. The most common genetic mutations in this disease are GJB2 mutations which are followed by SLC26A4 mutations. Following a report for the first time in the world insist on CABP2 gene interference in hearing loss production, the present study was launched to analyze this mutation in Iranian patients with hereditary hearing loss. METHODS: This is a cross sectional study. Among samples with autosomal recessive familial hearing loss pattern, regarding pedigree and audiometric data 253 patients with moderate to profound hearing loss were selected and studied. The mutation c. 637+1G>T was investigated using PCR-RFLP method. FINDINGS: PCR-RFLP findings revealed that c.637+1G>T mutation was absent in the deaf subjects with hereditary moderate to profound hearing loss in analyzed provinces. CONCLUSION: The mutation c.637+1G>T in CABP2 gene does not play any role in the investigated Iranian subjects with hereditary hearing loss. © 2014, Babol University of Medical Sciences. All rights reserved.

Associations between GJB2, Mitochondrial 12S rRNA, SLC26A4 Mutations, and Hearing Loss among Three Ethnicities

The epidemiological researches show that the mutations of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes have played an important role in the hearing loss. This study aims to investigate the mutation spectrum of GJB2, mitochondrial 12S rRNA, and SLC26A4 genes of Han Chinese, Hui people, and Uyghur ethnicities in sensorineural hearing loss (SNHL) patients in northwest of China. Mutational analyses in the three genes were brought by direct sequencing and each fragment was analyzed using an ABI 3730 DNA Sequencer. The mutation frequencies for the three HL causative genes were 34.05% in Han Chinese participants, 27.47% in Hui people, and 14.44% in Uyghur participants, respectively. The prevalence of GJB2 mutations was 13.7%, 11.4%, and 11.4% in Han Chinese, Hui people, and Uyghur participants (χ 2 = 10.2, P < 0.05), respectively. The prevalence of mtDNA 12S rRNA A1555G homozygous mutations was 6.05%, 3.27%, and 1.44% in Han Chinese, Hui people, and Uyghur participants (χ 2 = 13.9, P < 0.05), respectively. The prevalence of SLC26A4 mutations was 14.3%, 12.8%, and 1.6% in Han Chinese, Hui people, and Uyghur participants, respectively. In summary, we find that Uyghur and Hui SNHL individuals vary significantly from Han Chinese patients in three causative HL genes' mutational spectrum, especially for Uyghur.

Lethal Form of Keratitis–Ichthyosis–Deafness Syndrome Caused by the GJB2 Mutation p.Ser17Phe

Lethal Form of Keratitis–Ichthyosis–Deafness Syndrome Caused by the GJB2 Mutation p.Ser17Phe

Molecular Genetic Diagnosis of Deafness: Current and Future

Received April 7, 2013 Accepted June 20, 2013 Address for correspondence Byung Yoon Choi, MD Department of Otorhinolaryngology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea Tel +82-31-787-7406 Fax +82-31-787-4057 E-mail choiby@snubh.org Advances in molecular biology and molecular genetic technologies have revealed extreme etiologic heterogeneity of genetic hearing loss. Genes known to contribute to deafness have been reported to be involved with a variety of function and structures in the cochlea of the inner ear. Genetic alteration in deafness genes manifests hearing loss either in syndromic or in nonsyndromic forms, albeit much more frequently in latter forms. Molecular genetic diagnosis in this nonsyndromic hearing loss is challenging in majority of cases. GJB2 is the most frequent etiology of severe to profound nonsyndromic hearing loss in most of the ethnic backgrounds. When no potentially pathogenic GJB2 mutation is detected, characteristic audiogram profiles and radiologic markers help us to select next candidate deafness genes. Mutations in SLC26A4 and POU3F4 causes enlarged vestibular aqueduct and incomplete partition type III anomaly, respectively. TECTA, TMPRSS3, WFS1, COCH, KCNQ4 and DIAPH1 give rise to a characteristic audiologic configuration, if mutated. This phenotype-driven candidate gene approach has been successful not infrequently. With the advent of next generation sequencing technologies, molecular genetic diagnosis of hearing impaired subjects even without any characteristic markers is being widely tried. Targeted resequencing of known deafness genes appears to be effective in as high as 50-60% in making molecular genetic diagnosis at least for multiplex families where there are two or more affected hearing impaired subjects. Whole exome sequencing has been successful in revealing molecular genetic etiology anecdotally. More sophisticated pipeline and platform for revealing pathogenicity of detected variants both genetically and biologically is necessary to incorporate the advent of cutting edge sequencing technologies to the big step toward a personalized rehabilitation for hearing impaired subjects. Korean J Otorhinolaryngol-Head Neck Surg 2014;57:1-6

A novel compound heterozygous mutation in the GJB2 gene causing non-syndromic hearing loss in a family

Mutations in the GJB2 gene are responsible for up to 50% of cases of non-syndromic recessive hearing loss, with c.35delG, c.167delT and c.235delC being the predominant mutations in many world populations. However, a large number of rare mutations in this gene may also contribute to hearing loss. The aim of the present study was to conduct a clinical and molecular characterization of a Chinese family with non-syndromic hearing loss. Sequence analysis of the GJB2 gene led to the identification of a novel compound heterozygous mutation c.257C>G (p.T86R)/c.605ins46 in two profoundly deaf siblings whose hearing parents were each heterozygous, either for the c.257C>G (paternal) or for the c.605ins46 (maternal) mutations. Both c.257C>G and c.605ins46 are rare GJB2 mutations that have previously been reported to segregate with autosomal recessive hearing loss exclusively in East Asian populations. To study the pathogenic effect of the compound heterozygous mutation, a three-dimensional model was constructed and Anolea mean force potential energy was predicted for a bioinformatic structural analysis. HEK293 cells were used to study the pathogenic effect of mutant connexin 26 proteins. The results suggested that the c.257C>G (p.T86R)/c.605ins46 mutations in the GJB2 gene provides a novel molecular explanation for the role of the GJB2 gene in hearing loss.

GJB2 mutations are rare in probands with hearing loss in Chinese assortative mating families

ObjectiveGJB2 mutation is recognized as the prevalent causes of non-syndromic hearing loss (NSHL) worldwide. However, the mutation profiles of GJB2 are rarely reported in deafness probands of the assortative mating family. Therefore, this study aimed to characterize the frequencies of GJB2 mutations in probands with hearing loss in the assortative mating family in Hubei province, Central China. MethodsGenomic DNA was extracted from blood samples of 29 probands with hearing loss. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to sequencing to identify sequence variations. ResultsNone of 29 probands harbored homozygous mutation in GJB2, while GJB2 heterozygous mutations c.134G>A, c.139G>T, and a deletion c.235delC were identified in three probands, respectively. ConclusionGJB2 mutations are rare in Chinese probands of assortative mating families. Screening for responsible genes other than GJB2 is necessary for NSHL in these probands.

Genetic mutations in nonsyndromic deafness patients of Chinese minority and han ethnicities in Yunnan, China

BackgroundEach year in China, 30,000 babies are born with congenital hearing impairment. However, the molecular etiology of hearing impairment in the Yunnan Province population where more than 52 minorities live has not been thoroughly investigated. To provide appropriate genetic testing and counseling to these families, we investigated the molecular etiology of nonsyndromic deafness in this population.MethodsUnrelated students with hearing loss (n = 235) who attended Kunming Huaxia secondary specialized school in Yunnan enrolled in this study. Three prominent deafness-related genes, GJB2, SLC26A4 and mtDNA 12S rRNA, were analyzed. High-resolution temporal bone computed tomography (CT) scan examinations were performed in 100 cases, including 16 cases with SLC26A4 gene variants, and 37 minorities and 47 Han cases without any SLC26A4 gene mutation.ResultsThe GJB2 mutation was detected in 16.67% (7/42) of minority patients and 17.62% (34/193) of Chinese Han patients (P > 0.05). 235delC was the hotspot mutation in nonsyndromic hearing loss (NSHL) patients, whereas 35delG was not found. The 431_450del19 mutation was detected for the first time in Han NSHL patients, which resulted in a premature stop codon and changed the protein. The SLC26A4 mutation was found in 9.52% (4/42) of minority patients and 9.84% (19/193) of Han Chinese patients (P > 0.05). The frequencies of mtDNA 12S rRNA mutation in minority and Han Chinese patients were 11.90% (5/42) and 7.77% (15/193; P > 0.05), respectively. Sixteen (16/23, 69.57%) patients with SLC26A4 mutations received temporal bone CT scan, and 14 patients were diagnosed with enlarged vestibular aqueducts (EVAs); the other 2 patients had normal inner ear development. The ratio of EVA in the minorities was 14.63% (6/41).ConclusionsIn this study, a total of 35.74% deaf patients showed evidence of genetic involvement, based on either genetic screening or family history; 17.45%, 9.79%, and 8.51% of the patients were determined to have inherited hearing impairment caused by GJB2, SLC26A4, and mtDNA 1555A > G mutations. There was no significant difference in deafness associated gene mutational spectrum and frequency between the Yunnan minority and Han patients.