No Association between TNF-α -308G/A Polymorphism and Idiopathic Recurrent Miscarriage: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.

BACKGROUND: Conflicting results were reported on the association between the TNF-α -308G/A polymorphism and idiopathic recurrent miscarriage (IRM). Though three meta-analyses have been conducted on this topic, the conclusions were contradictory, and the results may be unreliable as certain crucial conditions were neglected. METHOD: A complete search was conducted in PubMed, Cochrane Library, and Embase, other sources like Google Scholar, ClinicalTrial.gov and reference lists of relevant articles were also retrieved. All candidate articles were accessed and screened using specific inclusion and exclusion criteria. Statistical analyses were performed on data extracted from eligible studies using the STATA 12.0 software and the TSA 0.9 beta software. RESULTS: Eventually, 12 case-control studies from 11 publications (with 1,807 cases and 2,012 controls) were included in this meta-analysis, and no evidence of any significant association was found in the overall analyses between the TNF-α -308G/A polymorphism and IRM risk. However, significant association was shown in Asian population (four studies from three publications) in the dominant model (AA + GA vs. GG), the allelic model (A vs. G), and the heterozygote model (GA vs. GG). CONCLUSIONS: TNF-α -308G/A polymorphism is not associated with IRM risk. Though significant association was found in Asian population, the result needs further confirmation from more studies.

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

OBJECTIVE: GJB2 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. METHODS: Genomic 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. RESULTS: None 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. CONCLUSION: GJB2 mutations are rare in Chinese probands of assortative mating families. Screening for responsible genes other than GJB2 is necessary for NSHL in these probands.

Otologic and audiologic characteristics of children with skeletal dysplasia in central China.

CONCLUSION: Otologic and audiologic abnormalities are both highly prevalent in Chinese children with skeletal dysplasias. Audiologic and otologic evaluations with medical intervention are recommended for these children. OBJECTIVE: Children with skeletal dysplasia have a number of otolaryngologic issues including hearing loss. This study aimed to investigate the otologic and audiologic features of Chinese children with skeletal dysplasia in central China. METHODS: Otologic evaluations and pure tone audiometry were performed in children with skeletal dysplasias. To explore the potential associations with hearing loss, we studied various craniofacial anomalies. RESULTS: A total of 125 children (mean age 9.2 years, range 5-18 years) with skeletal dysplasia were enrolled, and otoscopic examination identified eardrum abnormalities in 45.6% of the children. Audiologic analysis revealed 14 cases (11.2%) with conductive hearing loss (CHL) and 22 cases (17.6%) with sensorineural hearing loss (SNHL).

A large-scale newborn hearing screening in rural areas in China.

OBJECTIVES: Newborn hearing screening has been successfully implemented in cities of China, but not in rural areas. This study aimed to provide guidance on implementing hearing screening in the rural areas of China. METHODS: Subjects were 11,568 babies who were born in 5 counties of Hubei Province of China. Hearing screening followed a two-stage strategy with transient evoked otoacoustic emissions (TEOAEs). Infants referred after the second-stage screening were tested by diagnostic auditory brainstem response (ABR). RESULTS: The subjects screened included 10,665 (92.2%) normal newborns and 903 (7.8%) newborns with high-risk of hearing loss. While 8190 (70.8%) newborns passed the initial screening, 135 newborns failed in the re-screening, and 90 (66.7%) of these 135 newborns received diagnostic assessment. Finally, 58 infants were diagnosed as hearing loss, and the prevalence of congenital hearing loss among newborns in rural areas was 0.5% (58/11,568). CONCLUSIONS: This large-scale newborn hearing screening in rural areas of Hubei Province of China demonstrated that the screening rate and referral rate for high-risk infants are low. Urgent measures should be taken by the government to promote newborn hearing screening in the rural areas.

Prevalence of GJB6 mutations in Chinese patients with non-syndromic hearing loss.

OBJECTIVE: To investigate the distribution of GJB6 mutations in Central Chinese population with non-syndromic hearing loss. METHOD: Totally 655 hearing impaired patients in Hubei province of China were screened for del(GJB6-D13S1830) deletions by using multiplex PCR and sequencing of GJB6 whole coding region. RESULT: The del(GJB6-D13S1830) and other mutations in GJB6 gene were not observed in our study cohort. CONCLUSION: The results suggest that GJB6 mutations is not a common cause among Central Chinese population and screening for the mutations of GJB6 can be ranked as unconventional deaf gene test for this population.

Low frequency of GJB2 mutations in thirty-five students with hearing loss in Chinese consanguineous families.

OBJECTIVE: GJB2 mutation is recognized as the prevalent causes of non-syndromic hearing impairment (NSHI) worldwide. However, the mutation profiles of this gene are unknown in deafness probands in the consanguineous pedigrees in China. Therefore, this study aimed to characterize the forms and frequencies of GJB2 mutations in 35 students with hearing loss in the consanguineous families in Hubei province, Central China. METHODS: Genomic DNA was extracted from blood samples of 35 students with hearing loss. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to sequencing to identify sequence variations. RESULTS: Surprisingly, none of these probands harbored homozygous mutation in GJB2. Three GJB2 heterozygous mutations were identified: a single base pair substitution c.35G>T and c.139G>T, and a 2 bp deletion c.299-300delAT in three probands. CONCLUSION: The frequency of GJB2 mutation is relatively low in these consanguineous families, most of which were minorities. Our results suggest that screening for responsible genes other than GJB2 may be necessary for NSHI in these minorities.

GJB2 and mitochondrial DNA 1555A>G mutations in students with hearing loss in the Hubei Province of China.

OBJECTIVES: The GJB2 and MTRNR1 1555A>G mutations are the prevalent causes of hearing loss worldwide. However, the mutation profiles of the two genes are dependent on the ethnic or geographic origins. Therefore, this study was to characterize the forms and frequencies of the two genes in 813 students with hearing loss in Hubei province, Central China. METHODS: Blood samples from 813 students were obtained with informed consent. Genomic DNA was extracted from peripheral blood leukocytes. The target fragments were amplified by polymerase chain reaction (PCR). Sequencing (or enzyme digestion) was applied to identify sequence variations. RESULTS: Ten different mutations were identified in GJB2 in 146 of the 813 (17.96%) patients and 11.81% (96/813) patients had homoplasmic mtDNA 1555A>G mutation. CONCLUSIONS: This study demonstrated the high prevalence of GJB2 and mtDNA 1555A>G mutations in Central Chinese population. Therefore, it will be effective to perform GJB2 and mtDNA 1555A>G mutation analysis for genetic screening for hearing loss in this population.

The audiological characteristics of a hereditary Y-linked hearing loss in a Chinese ethnic Tujia pedigree.

OBJECTIVE: To investigate audiometric characteristics of hearing loss in a large Chinese ethnic Tujia family and determine its hereditary type. METHODS: Total 76 live individuals were investigated in the notable 84 members of this family. The detailed audiometric evaluations were undertaken for the proband and his 47 family members. The degrees of sensorineural hearing impairment were defined as an air/bone gap <15dB hearing loss averaged over 0.5, 1 and 2kHz. The severity of hearing loss was established based on the hearing ability of the better ear, averaged over 0.5, 1, 2 and 4kHz, and classified into four categories: mild, moderate, severe and profound. RESULTS: Nineteen patrilineal relatives of the 76 live members had hearing impairment. The age of onset ranged from 7 to 21 years old with the average of 13.2 years. The audiometric defect was described by auditory curves of a high frequency in 47% of the patients. Affected members in this family demonstrated a non-syndromic, late onset, bilateral, symmetrical, postlingual and sensorineural hearing loss. CONCLUSIONS: The audiometric configuration in males of the pedigree is consistent with the hereditary Y-linked hearing loss. Thus we speculate that a putative gene on the Y chromosome could contribute to the cause of the disease.

Parental attitudes toward genetic testing for prelingual deafness in China.

OBJECTIVE: Recent advances in molecular biology of hearing and deafness have made genetic testing an option for deaf individuals and their families. In China, DNA microarray and other genetic testing method has been applied to rapid genetic diagnosis of non-syndromic hearing loss. However, there is no information about the interests in such testing in China. The purpose of this study is to document the attitudes of parents with normal hearing who have one or more deaf children toward diagnostic, carrier, and prenatal genetic testing for deafness. METHODS: A structured, self-completion questionnaire was given to delegates at a conference held at Hubei Rehabilitation Research Center for Deaf Children, Wuhan, China on March 3, 2010. Of 366 surveys distributed, 290 were completed and returned. RESULTS: Ninety-four percent of the respondents had a positive attitude toward genetic testing. Seventy-two percent stated that they were interested in genetic testing of deaf child. Of the individuals who were interested in such testing, 69% would consider having prenatal genetic testing for deafness. CONCLUSION: The present study provided evidence of a predominantly positive attitude toward genetics. Appropriate genetic counseling can help parents to understand the risk, benefits, and limitations of genetic testing for prelingual deafness.

Prevalence and etiology of hearing loss in primary and middle school students in the Hubei Province of China.

The purpose of this study was to investigate the prevalence and etiology of hearing loss in primary and middle school students in the Hubei province of China. During a 2-year period, 504348 students were examined by a speech audiometry test, and 813 deaf students were detected. Among the 813 deaf students, 232 cases were diagnosed with congenital deafness and 560 cases had acquired deafness, among which 276 cases had aminoglycoside-antibiotic-induced deafness. The severity of deafness could be further ascertained in 804 other students, with 402 profound, 363 severe, 21 moderate and 18 mild deafness cases. The age at deafness onset of most students was under 3 years. The prevalence of congenital and acquired deafness was 0.046% (232/504348) and 0.111% (560/504348), respectively, much lower than previously reported in other regions of China. Furthermore, the genetic factor was identified as one of the principal causes of deafness by pedigree analysis.