The research progress of unilateral enlargement of the vestibular aqueduct / 临床耳鼻咽喉头颈外科杂志

Unilateral enlargement of the vestibular aqueduct (EVA)is a relatively rare disease. Bilateral EVA was found to be more common than unilateral EVA. There are significant differences in clinical features and molecular etiology between unilateral EVA and bilateral one. This article reviewed related researches of the unilateral EVA in clinical characteristics, molecular etiology and pathogenic mechanism.

The study of GJB2 dominant mutaion distribution in Chinese deafness patient and the analysis of phenotype / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Mutations in the GJB2 are the most common cause of nonsyndromic autosomal recessive sensorineural hearing loss. A few mutations in GJB2 have also been reported to cause dominant nonsyndromic or syndromic hearing loss. This study analysised the GJB2 dominant mutation in Chinese deafness.@*METHOD@#1641 patients as GJB2-related hearing loss were enrolled, summarized the type of dominant mutaion, analyzed the hearing level and other systerm lesion.@*RESULT@#Nine probands with severe-profound hearing loss were diagnosed as GJB2 domiant mutation (R75W,G130V, R143Q,p. R184Q). And one patient with R75W mutation was diagosed as hearing loss and palmoplantar keratoderma.@*CONCLUSION@#GJB2 dominant mutation can cause severe-to-profound bilateral sensorineural hearing impairment and not common with syndromic hearing loss in Chinese deafness.

Assessment of the curative effective of cochlear implantation in childer with GJB2-associated NSSNHL / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the curative effect of CI in children with GJB2-associated NSSNHL.@*METHOD@#The evaluations of curative effect with CI include auditory threshold, IT-MAIS/MAIS, CAP, SIR. MESP. The outcomes of 40 cases with GJB2-associated NSSNHI, were compared 80 patients with negative results of screening of gene mutation (control group).@*RESULT@#In comparison with control group the auditory threshold in children with GJB2-associated NSSNIL is better, however had no significant difference in other tests (P > 0.05).@*CONCLUSION@#CI could he performed on children with GJB2-associated NSSNHL. Postoperative outcomes of hearing and speech were satisfied.

Investigation of SLC26A4 mutations associated with inner ear malformations / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the molecular pathogenesis of SLC26A4 mutations associated with inner ear malformations including large vestibular aqueduct syndrome (LVAS), Mondini dysplasia and inner ear malformations but not accompanied with LVAS.@*METHOD@#DNA sample and clinical material were obtained from 14 sporadic LVAS probands, six Mondini dysplasia probands and seven inner ear malformations excluding IVAS probands. SLC26A4 gene mutation was analyzed by direct sequencing for its 20 coding exons. GJB2 gene and also mt12SrRNA were analyzed by direct sequencing.@*RESULT@#In 14 cases of LVAS, two mutations were detected in 12 patients (85.7%, either homozygous or compound heterozygous mutations), and one mutation was found in two patients (14.3%). In six cases of Mondini dysplasia, two mutations were detected in all of patients (100%). No mutation could be found in the seven cases of other inner ear abnormalities not accompanied with LVAS. No pathogenic mutation was detected in all of these 27 probands in GJB2 gene and mt12SrRNA 1555/1494T.@*CONCLUSION@#We have shown that LVAS and Mondini dysplasia closely correlate with SLC26A4 gene. No mutation was detected in seven probands of inner ear malformations not accompanied with LVAS. We should study the molecular pathogenesis of this disease in depth.

Retrospective analysis of the treatment of recurrent congenital fistula or cyst in lateral cervical part / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analysis the therapeutic procedure on the recurrent congenital fistula or cyst in lateral cervical part.@*METHOD@#Thirty-nine cases with recurrent congenital fistula or cyst in lateral cervical part were enrolled in this study including 12 cases from the first branchial cleft, 6 from the second branchial cleft and 21 from the third branchial cleft.@*RESULT@#All the cases underwent fistula or cyst excision for 2 to 5 times in their whole therapeutic process, not counting the incision and drainage. During 9 months to 17 years follow-up, fistula or cyst in 6 cases relapsed,including 1 fistula from the first branchial cleft,3 fistulae from the second branchial cleft, 1 fistula and 1 cyst from the third branchial cleft, respectively. One case with recurrent fistula from the first branchial cleft was diagnosed temporal verrucous carcinoma six months after the third fistula excision operation and died one year after the forth operation probably due to the intracranial metastasis of temporal bone verrucous carcinoma. In two cases, the fistulae went through the thyroid gland to the piriform fossa and both the fistulae and part of the thyroid glands were resected. In the patients whose inner orificium fistulae were found and ligated effectively,no recurrence occurred during the followed-up period.@*CONCLUSION@#The key point to cure the recurrent congenital fistula or cyst in lateral cervical part lies in proper occasion of operation, stain tracing in operation and reasonable program of operation.

Analysis of positive rate of common genetic mutations in 1448 cases with different hearing phenotype / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the positive rate of common genetic mutations in Chinese non-syndromic sensorineural hearing loss groups with different hearing phenotype.@*METHOD@#One thousand four hundred and forty-eight subjects with hearing test results received at least one of three genetic testings including: mutations in coding region of GJB2 and SLC26A4 with sequencing analysis and mitochondrial DNA C1494T/A1555G with microarray detection. Of 1448 subjects, 1333 have bilateral sensorineural hearing loss, 65 have unilateral hearing loss and 50 have normal hearing threshold even though they have high frequency hearing loss or family history. The informed consent of each subject was achieved.@*RESULT@#Mutation positive rate of GJB2, SLC26A4 and mtDNA C1494T/ A1555G of 1448 subjects were 19.23%, 27.55%, 0.1% and 1.72% respectively. The positive rate of GJB2 and SLC26A4 mutations in bilateral hearing loss group (20.22%, 29.17%) was statistically significantly higher than unilateral group (0, 0) (P < 0.01). In bilateral hearing loss group, the positive rate of GJB2 mutations was highest in the profound group (24.67%), and then severe (22.33%), moderate (14.33%) and mild group (6.58%) (P < 0.01). The positive rate of SLC26A4 mutations was highest in the severe group (48.67%), and then profound (28.42%), moderate (21.16%) and mild (8.93%) (P < 0.01).@*CONCLUSION@#The positive rate of GJB2 and SLC26A4 mutations is high in the groups with bilateral profound and severe sensorineural hearing loss, whose genetic testing should be put emphasis on. However, the genetic testing should be performed in patients with mild to moderate hearing impairment as well if necessary.

Mutation analysis of GJB2, GJB3 and GJB6 gene in deaf population from special educational school of Chifeng city / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the genetic causes of nonsyndromic deaf patients in special educational school of Chifeng city. Inner Mongolia by genetic screening testing method. This study focused on analyzing mutations of coding sequence of GJB2, GJB3 and GJB6 gene.@*METHOD@#DNA were extracted out from peripheral blood of 134 nonsyndromic deaf probands of Chifeng special educational school and 100 normal hearing controls in northern China. First, GJB2 gene mutation was analyzed by direct sequencing for its only exon in the open reading frame. Individuals found with heterozygous GJB2 mutation were given further testing for GJB6 del(GJB6-D13S1830) and direct sequencing for its exon. In 91 probands with unknown genetic cause (excluding probands who carried mtDNA A1555G mutation and GJB2 gene bi allele mutation and probands who were diagnosed as enlarged vestibular aqueduct by temporal CT), GJB3 gene mutation was analyzed by direct sequencing for its exon.@*RESULT@#The sequencing results revealed that forty-one cases carried GJB2 mutation. of which twenty-two were homozygous or compound heterozygous and nineteen were heterozygous. Further testing for GJB6 del(GJB6-D13S1830) and analysis of its coding sequence in GJB2 heterozygous cases showed no positive result. Four subjects in control group carried pathogenetic mutation of GJB2 gene. Six types of novel variants of GJB2 gene were detected. Of the 91 deaf probands with unknown etiology. two probands were found carrying heterozygous pathogenetic mutation of GJB3 gene. one of whom also carried GJB2 235delC heterozygous mutation. One subjects in the control group carried pathogenetic mutation of GJB3 gene. Three types of novel variants of GJB3 gene were found.@*CONCLUSION@#By screening GJB2.GJB3 and GJB6 gene, we found 32.1% probands carrying GJB2, GJB3, and GJB6 mutations and we are able to determine genetic cause related to these three genes from one family for 16.42 percent of nonsyndromic deaf probands in special educational school of Chifeng city. The discovery of novel variants of GJB2 and GJB3 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population.

GJB6 gene mutation analysis in Chinese nonsyndromic deaf population / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the contribution of GJB6 gene (encoding connexin 30) mutation in Chinese population with sporadic non-syndromic hearing impairment.@*METHOD@#Three hundred and seventy-two nonsyndromic hearing impairment patients and 182 normal controls were first tested for GJB6 del(GJB6 > D13S1830) using specific PCR primers. Then PCR was performed with a pair of primer flanking the whole coding sequence of GJB6 gene. Sequencing of GJB6 whole coding sequence PCR products was subsequently applied in all subjects with hearing loss and normal controls.@*RESULT@#None of the patients and normal controls carried GJB6 del (GJB6 > D13S1830). Two single base pair changes were detected , one in the patient group and the other in the control group. The mutation found in the patient group was not detected in the control subjects.@*CONCLUSION@#Mutation of GJB6 gene is not frequent in Chinese non-syndromic hearing-loss population. Screening for GJB6 gene can be ranked as unconventional deaf gene test in China temporarily.

Genotypic and phenotypic analysis of SLC26A4 gene in deaf patients of Chifeng area by whole gene sequencing strategy / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the genetic causes of deaf patients in a special educational school of Chifeng city, Inner Mongolia by SLC26A4 whole gene sequencing. This study focused on analyzing mutations of coding sequence of SLC26A4 gene and their relevant phenotype. METHODS DNA were extracted from peripheral blood of 134 deaf patients of Chifeng special educational school and 100 normal hearing controls in Northern China. SLC26A4 gene mutation was analyzed by direct sequencing for its 20 coding exons. All individuals found with SLC26A4 mutation were given temporal bone CT scan, and those with confirmed enlarged vestibular aqueduct and/or other malformation of inner ear were then given further ultrasound scan of thyroid and thyroid hormone assays. RESULTS The sequencing results revealed 32 cases carried SLC26A4 mutation. Twenty-nine cases underwent temporal bone CT scan. Twentycases were confirmed to have malformation of inner ear by CT scan (eighteen were EVA, one was EVA and other inner ear malformation and one was Mondini Syndrome). The shape and function of thyroid were confirmed to be normal by ultrasound scan of thyroid and thyroid hormone assays in nineteen of these 20 patients except one who had cystoid change in the right side of thyroid. Twelve types of novel variants of SLC26A4 gene were found. CONCLUSION Byscreening SLC26A4 gene coupled with temporal bone CT scan ,we could determine genetic cause related to this gene up to 14.93 % of deaf patients in special educational school of Chifeng city. SLC26A4 is another common gene besides GJB2 that cause deafness in this area. The discovery of novel variants of SLC26A4 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population.

Mitochondrial DNA and GJB2 Genovariation in Noise-Induced Hearing Loss in the Army / 听力学及言语疾病杂志

Objective To explore the relationship between mitochondrial DNA gene,GJB2 gene mutations and the susceptibility to noise-induced hearing loss in the army,and to provide scientific evidence for gene screening of susceptible individuals and relevant molecular epidemiology.Methods 182 blood samples were collected from 349 soldiers,consisting of susceptible and tolerance groups exposed to military noise in Beijing.Genomic DNA was isolated,and the targeted fragments of mitochondrial DNA and coding region of GJB2 gene were amplified by polymerase chain reaction(PCR).The PCR products were analyzed by direct sequencing.Results The results revealed that there were 98 mtDNA variants(41 reside in 12SrRNA) and 12 GJB2 gene variants;among them,mtDNA T1095C and G7642A coexisted in 4 susceptible individuals,but these mutations were not found in the tolerance group.In addition,3 tolerant individuals carried 961delT+insC while no one was found in the susceptible group.Conclusion The 12SrRNA is an area evidenced by high variant and mutation rate.The coexistence of mtDNA T1095C and G7642A in the susceptible group exposed to the similar noise suggests that these mutations are pathogenic mutations associated with NIHL.Three tolerant individuals with the history of long-term noise exposure carry 961delT+insC,suggesting that 961delT+insC might be a conditional pathogenic mutation,but not correlate with NIHL.