Prevalence of the GJB2 IVS1+1G >A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2

<p>Abstract</p> <p>Background</p> <p>Mutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic <it>GJB2 </it>mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the <it>GJB2 </it>IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of <it>GJB2</it>.</p> <p>Methods</p> <p>Two hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of <it>GJB2 </it>were examined for the <it>GJB2 </it>IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without <it>GJB2 </it>mutation and 105 controls with normal hearing were also tested for the <it>GJB2 </it>IVS1+1G>A mutation by sequencing.</p> <p>Results</p> <p>Four patients with monoallelic mutation in the coding region of <it>GJB2 </it>were found carrying the <it>GJB2 </it>IVS1+1G>A mutation on the opposite allele. One patient with the <it>GJB2 </it>c.235delC mutation carried one variant, -3175 C>T, in exon 1 of <it>GJB2</it>. Neither <it>GJB2 </it>IVS1+1G>A mutation nor any variant in exon 1 of <it>GJB2 </it>was found in the 262 nonsyndromic hearing loss patients without <it>GJB2 </it>mutation or in the 105 normal hearing controls.</p> <p>Conclusion</p> <p>Testing for the <it>GJB2 </it>IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese <it>GJB2 </it>monoallelic patients, and it should be included in routine testing of patients with <it>GJB2 </it>monoallelic pathogenic mutation.</p

Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>SLC26A4 </it>cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity). The relationship between mutations in <it>SLC26A4 </it>and Mondini deformity without enlarged vestibular aqueduct has not been studied in any Chinese deaf population. The purpose of this study was to assess whether mutations in the <it>SLC26A4 </it>gene cause Mondini deformity without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese population.</p> <p>Methods</p> <p>In total, 144 patients with sensorineural hearing loss were included and subjected to high-resolution temporal bone CT. Among them, 28 patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16 patients with other types of inner ear malformations (IEM group) were identified. The coding exons of <it>SLC26A4 </it>were analyzed in all subjects.</p> <p>Results</p> <p>DNA sequence analysis of <it>SLC26A4 </it>was performed in all 144 patients. In the different groups, the detection rate of the <it>SLC26A4 </it>mutation differed. In the isolated MD group, only one single allelic mutation in <it>SLC26A4 </it>was found in one patient (1/28, 3.6%). In the EVA with MD group, biallelic and monoallelic <it>SLC26A4 </it>mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. Also, in the EVA group, biallelic and monoallelic <it>SLC26A4 </it>mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. These percentages were identical to those in the EVA plus MD group. Only two patients carried monoallelic mutations of the <it>SLC26A4 </it>gene in the IEM group (2/16, 12.5%). There were significant differences in the frequency of <it>SLC26A4 </it>mutation among the groups (P < 0.001). The detection rate of <it>SLC26A4 </it>mutation in the isolated MD group was significantly lower than in the EVA group (with or without MD; P < 0.001), and there was no significant difference in the detection rate of <it>SLC26A4 </it>between the MD group and IEM group (P > 0.5).</p> <p>Conclusion</p> <p>Although mutations in the <it>SLC26A4 </it>gene were frequently found in Chinese EVA patients with and without MD, there was no evidence to show a relationship between isolated MD and the <it>SLC26A4 </it>gene in the Chinese population examined. Hearing impairment in patients with isolated MD may be caused by factors other than mutations in the <it>SLC26A4 </it>gene.</p

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 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

Microseepage of methane to the atmosphere from the Dawanqi oil-gas field, Tarim Basin, China

The microseepage of natural gas from subsurface hydrocarbon reservoirs is a widespread process in petroleum basins. On a global scale, microseepage represents an important natural source of atmospheric methane (CH4). To date, microseepage CH4 flux data have been obtained from ~20 petroleum systems in North America, Europe, and Asia. While the seasonal variations of gas flux due to soil methanotrophic activity are known, the role of geological factors in controlling gas fluxes has been poorly investigated. Here we present new microseepage data from the Dawanqi oil-gas field located within the Tarim Basin (China), a petroleum system characterized by intense faulting and shallow (<700 m) reservoirs. We measured CH4 fluxes from the ground at 51 sites along three transects by using a closed-chamber connected to a portable gas sensor using off-axis integrated cavity output spectroscopy. Our results indicate that the highest CH4 fluxes occur over faults and/or shallow reservoirs, especially those that were not developed and that have higher fluid pressures. Microseeping CH4 is thermogenic, like that occurring within the Dawanqi reservoirs, as demonstrated by 13C enrichment (δ13C from 46.3‰to 30.7‰) in the chamber. Mean and range microseepage values (17 mg m 2d 1; from 1.4 to 330 mg m 2d 1) are similar to those reported for other petroleum fields with active tectonics. Our results confirm that dry soil over petroleum fields can be a net source of atmospheric CH4 and its flux is primarily controlled by faulting, and reservoir depth and pressure. These factors shall be considered in global bottom-up seepage emission estimates.Published4353–43636A. Geochimica per l'ambienteJCR Journa

<it>SLC26A4</it> gene copy number variations in Chinese patients with non-syndromic enlarged vestibular aqueduct

<p>Abstract</p> <p>Background</p> <p>Many patients with enlarged vestibular aqueduct (EVA) have either only one allelic mutant of the <it>SLC26A4</it> gene or lack any detectable mutation. In this study, multiplex ligation-dependent probe amplification (MLPA) was used to screen for copy number variations (CNVs) of <it>SLC26A4</it> and to reveal the pathogenic mechanisms of non-syndromic EVA (NSEVA).</p> <p>Methods</p> <p>Between January 2003 and March 2010, 923 Chinese patients (481 males, 442 females) with NSEVA were recruited. Among these, 68 patients (7.4%) were found to carry only one mutant allele of <it>SLC26A4</it> and 39 patients (4.2%) lacked any detectable mutation in <it>SLC26A4</it>; these 107 patients without double mutant alleles were assigned to the patient group. Possible copy number variations in <it>SLC26A4</it> were detected by SALSA MLPA.</p> <p>Results</p> <p>Using GeneMapper, no significant difference was observed between the groups, as compared with the standard probe provided in the assay. The results of the capillary electrophoresis showed no significant difference between the patients and controls.</p> <p>Conclusion</p> <p>Our results suggest that CNVs and the exon deletion in <it>SLC26A4</it> are not important factors in NSEVA. However, it would be premature to conclude that CNVs have no role in EVA. Genome-wide studies to explore CNVs within non-coding regions of the <it>SLC26A4</it> gene and neighboring regions are warranted, to elucidate their roles in NSEVA etiology.</p

Internal hernia through hepatic falciform ligament iatrogenic defect in a neonate: A case report and review of the literature

Internal hernia through an iatrogenic defect in the hepatic falciform ligament and acquired jejunal atresia in a 8-day-old neonate was reported. The PubMed, MEDLINE, CNKI, Wanfang and Weipu databases were searched The literature about the hepatic falciform ligament iatrogenic defect causing internal hernia was analysed. Ten other cases were collected from the world literature. Herniated intestinal necrosis was found in four cases. All cases were recovered uneventfully after operation. Internal herniation through an iatrogenic defect in the hepatic falciform ligament is extremely rare. However, the case reports are increasing, especially in the era of laparoscopic surgery. Adequate closure or open the defect is essential to prevent internal hernia occurrence