Screening for hotspot mutations associated with genetic hearing impairment in pregnant women and subsequent prenatal diagnosis in high risk pregnancies / 中华耳鼻咽喉头颈外科杂志

Objective@#To screen for hotspot gene mutations associated with genetic deafness in Chinese pregnant women, and to perform risk assessment and prenatal diagnosis in high-risk families.@*Methods@#Between November 2012 and October 2017, 26 117 pregnant women were screened by molecular hybridization microarray for 9 hot-spot mutations in 4 hereditary deafness related genes (GJB2 c. 35 del G, c. 176_191 del 16 bp, c. 235 del G, c. 299_300 del AT, GJB3 c. 538 C>T, SLC26A4 c. 2168 A>G, IVS 7-2 A>G, mitochondrial DNA 12S rRNA m. 1494 C>T, m. 1555 A>G). Genotype analysis was carried out in husbands of women carrying mutations, and prenatal diagnosis was carried out in the fetuses with high risk of deafness.@*Results@#Among all women tested, 1 208(4.63%) were carriers of genetic deafness mutations, 7 with hearing impairment were affected by homozygous or compound heterozygous mutations, 51 were mitochondrial gene mutation carriers, 103 were carriers of GJB3 c. 538 C>T heterozygous mutation, 1 026 were carriers of GJB2 or SLC26A4 heterozygous mutations, and 21 carried heterozygous mutations in two genes simultaneously. In 394 families, the husbands accepted gene sequence testing, and 27 in which were determined as carriers of mutations in identical genes as their wives. Among which, 18 families received prenatal diagnosis, and 5 fetuses were diagnosed as hereditary deafness. In 9 families who did not receive prenatal diagnosis, 1 neonate was diagnosed as compound heterozygote after delivery.@*Conclusion@#In order to prevent birth defects with congenital hearing problems, it is effective to provide screening for hotspot mutations in pregnant women and to perform prenatal diagnosis on high risk pregnancies.

Audiological Characteristics in 832 Deaf Children with Biallelic Causative Mutations in GJB2,SLC26A4 Gene / 听力学及言语疾病杂志

Objective To determine the audiological characteristics in 832 deaf children with biallelic causative mutations in GJB2 ,SLC26A4 gene .Methods The 832 patients received deafness gene screening ,553 were GJB2 gene biallelic causative mutations ,279 were SLC26A4 gene biallelic causative mutations .Patients were divided into four groups according to ages of hearing loss onset :<1 ,1~3 ,3~6 ,6~12 years old ,and the audiological character-istics and prevalence of GJB2 ,SLC26A4 gene mutations at different ages of onset .Results The prevalence of GJB2 gene mutations at four groups was 37 .97% (210/553) ,38 .34% (212/553) ,16 .27% (90/553) ,7 .41% (41/553) ,re-spectively ;the prevalence of SLC26A4 gene mutations at four groups was 25 .45% (71/279) ,44 .80% (125/279) , 20 .07% (56/279) ,9 .67% (27/279) ,respectively .The difference between GJB2 and SLC26A4 gene was significant(P=0 .001) .The prevalence of profound hearing loss with GJB2 gene mutations at four groups were 66 .67% (140/210) ,61 .32% (130/212) ,47 .78% (43/90) ,41 .46% (17/41) ,respectively .The difference was significant (P=0 .004) ,while the difference in 279 patients with SLC26A4 gene mutations was not statistically significant (P= 0 . 083) .Conclusion The age of hearing loss onset in patients with biallelic causative mutations in GJB 2 or SLC26A4 gene refers to 0~3 years -old ,hearing loss in patients with GJB2 ,SLC26A4 gene mutations gives priority to pro-found .The age of hearing loss onset is smaller ,the ratio of profound hearing loss is higher .Patients with severe and profound hearing impairment should be performed the genetic testing when the age of onset under 12 .

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.

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.

Molecular etiology of 573 patients with nonsyndromic hearing loss in 5 provinces of northwest region of China / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the prevalence of an A-to-G mutation at nucleotide 1555 of the mitochondrial genome in patients with nonsyndromic hearing impairment (NSHI) of northwest region of China.@*METHOD@#A standardized program of epidemiological design, administrative support, sample collection and mutation screening for mtDNA 12SrRNA A1555G were used performed to study the general condition and the molecular etiology of patients with severe to profound hearing loss from 5 provinces of northwest region of China.@*RESULT@#Five-hundred-seventy-three cases with severe profound hearing loss from 5 provinces were collected and 31 cases were found to carry mtDNA 12SrRNA A1555G mutation.@*CONCLUSION@#Among the patients with severe to profound hearing loss from 5 provinces of northwest region, there was a high proportion of hereditary hearing impairment caused by mtDNA 12SrRNA A1555G mutation. Screening and testing for this mutation are effective methods to prevent ototoxicity in A1555G carriers and their maternal family members.

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.

Genetic testing for the enlarged vestibular aqueduct syndrome and mutation analysis of the SLC26A4 gene / 中国耳鼻咽喉头颈外科

T,and 916-917 ins G were SLC26A4 mutations unreported hitherto, which may be specific to the Chinese population. CONCLUSION The EVA syndrome is a typical autosomal recessivehereditary disease caused by mutations in SLC26A4 gene. Genetic testing of SLC26A4 is the one of the important diagnostic methods for EVA syndrome.