Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.
We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions.
We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis.
Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed.
Acromioclavicular dislocations are very common shoulder injuries. The optimal treatment for acute high-grade acromioclavicular joint injury remains a matter of debate. The purpose of this study was to evaluate the results of surgical treatment of complete acromioclavicular dislocation using coracoid process transfer and temporary K-wire transfixation. Twenty-one patients with complete acromioclavicular dislocation underwent coracoid process transfer and temporary K-wire transfixation. Patients were assessed at the follow-up based on visual analog scores (VAS), the Constant–Murley scoring system and the UCLA shoulder rating system. Radiographs were taken to check up vertical instability. The mean follow-up was 32.1 months (25–47 months). The mean Constant and Murley score and UCLA shoulder rating score was 89.9 ± 8.4 and 30.1 ± 4.4. There were fourteen excellent functional results and six results and one poor result. The overall rate of satisfaction, which means an excellent or good result, was 95.2 %. Nineteen patients (90.4 %) maintained their previous jobs or resume their daily activities. The mean final pain score, as measured from 1 to 10 on the visual analog scale, was 1.91 ± 1.09. The radiographic analysis revealed twenty patients had maintained reduction at the final follow-up. The coracoid process transfer and temporary K-wire transfixation is a reliable treatment for a complete acromioclavicular dislocation.
Coracoid process transfer; Acromioclavicular dislocation; K-wire
Salix matsudana Koidz. is a deciduous, rapidly growing, and drought resistant tree and is one of the most widely distributed and commonly cultivated willow species in China. Currently little transcriptomic and small RNAomic data are available to reveal the genes involve in the stress resistant in S. matsudana. Here, we report the RNA-seq analysis results of both transcriptome and small RNAome data using Illumina deep sequencing of shoot tips from two willow variants(Salix. matsudana and Salix matsudana Koidz. cultivar ‘Tortuosa’). De novo gene assembly was used to generate the consensus transcriptome and small RNAome, which contained 106,403 unique transcripts with an average length of 944 bp and a total length of 100.45 MB, and 166 known miRNAs representing 35 miRNA families. Comparison of transcriptomes and small RNAomes combined with quantitative real-time PCR from the two Salix libraries revealed a total of 292 different expressed genes(DEGs) and 36 different expressed miRNAs (DEMs). Among the DEGs and DEMs, 196 genes and 24 miRNAs were up regulated, 96 genes and 12 miRNA were down regulated in S. matsudana. Functional analysis of DEGs and miRNA targets showed that many genes were involved in stress resistance in S. matsudana. Our global gene expression profiling presents a comprehensive view of the transcriptome and small RNAome which provide valuable information and sequence resources for uncovering the stress response genes in S. matsudana. Moreover the transcriptome and small RNAome data provide a basis for future study of genetic resistance in Salix.
Atonal homolog 1 (Atoh1) is crucial to the differentiation of many cell types and participates in tumorigenesis and progression. However, the expression of Atoh1 in gastrointestinal stromal tumors (GIST) and its relationship to clinical characteristics of this disease remain poorly understood. In this study, immunohistochemical analysis using tissue microarray (TMA) was employed to evaluate the expression of Atoh1 in GIST and the correlation between Atoh1 expression and clinicopathological features of GIST as well as patient outcome. High Atoh1 cytoplasmic expression was observed in 77.22% of patients with GIST, which was related to the mitotic index (P = 0.010) and AFIP-Miettinen risk classification (P = 0.045). High Atoh1 nuclear expression was seen in 69.49% of cases, which was associated with mitotic index (P = 0.003) and AFIP-Miettinen risk classification (P = 0.001). The Kaplan-Meier method and log-rank test indicated that high Atoh1 cytoplasmic expression, high Atoh1 nuclear expression, small tumor diameter, low mitotic index and TNM stage significantly correlated with improved survival of GIST patients. Overall, the data suggest that Atoh1 high expression correlates with a good prognosis and it may serve as a favorable prognostic factor for GIST. These results also support a role for Atoh1 as a tumor suppressor gene in GIST.
Atoh1; GIST; tissue microarray; immunohistochemistry; prognosis
The aim of the present study was to summarize and analyze the complications of posterior vertebral column resection in patients with spinal tumors. The complications of 40 patients following surgery were recorded, and surgery-related parameters including segments, bleeding volume and surgical duration were recorded and analyzed. SPSS 12.0 software was used to analyze the correlation between the complications and these parameters retrospectively. A total of 36 complications were reported. The median follow-up duration of the patients was 14 months (range, 4–78 months). Transient late tracheal extubation was associated with higher intraoperative bleeding volume, lower preoperative forced vital capacity and forced expiratory volume in 1 sec. Replaced spinal segment subsidence was associated with increased duration of surgery, higher intraoperative bleeding volume and higher total blood transfusion volume. Thrombocytopenia was associated with increased duration of surgery and higher total blood transfusion volume. The majority of the complications were minor and did not affect the recovery of the patients. Active prevention is necessary to reduce the incidence of complications, in particular, major ones.
vertebral column resection; spinal tumor; complication
Populus (Salicaceae) is one of the most economically and ecologically important genera of forest trees. The complex reticulate evolution and lack of highly variable orthologous single-copy DNA markers have posed difficulties in resolving the phylogeny of this genus. Based on a large data set of nuclear and plastid DNA sequences, we reconstructed robust phylogeny of Populus using parsimony, maximum likelihood and Bayesian inference methods. The resulting phylogenetic trees showed better resolution at both inter- and intra-sectional level than previous studies. The results revealed that (1) the plastid-based phylogenetic tree resulted in two main clades, suggesting an early divergence of the maternal progenitors of Populus; (2) three advanced sections (Populus, Aigeiros and Tacamahaca) are of hybrid origin; (3) species of the section Tacamahaca could be divided into two major groups based on plastid and nuclear DNA data, suggesting a polyphyletic nature of the section; and (4) many species proved to be of hybrid origin based on the incongruence between plastid and nuclear DNA trees. Reticulate evolution may have played a significant role in the evolution history of Populus by facilitating rapid adaptive radiations into different environments.
Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients.
Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database.
Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG.
First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.
Breast cancer is one of the most common cancer and remains the leading cause of cancer-related deaths in women. There is increasing evidence suggesting that TRPM7 plays a pivotal role in breast cancer progression and metastasis. In this study, a case–control study was carried out to investigate the effects of SNPs in TRPM7 genes in the development of breast cancer in Han Population of Northeast China. A total of six SNPs (rs8042919, rs4775899, rs11635825, rs7173321, rs616256, and rs11070795) were chosen and genotyped. Genotypes were analyzed using a single-base primer extension assay. Chi-square (χ2) test was used to analyze statistical difference between control and patient groups in genotype and allele frequencies. The genotype-specific risks and allele frequencies of haplotypes in breast cancer patients and controls were estimated by OR and 95 % confidence intervals. The G allele of rs8042919 was associated with a reduced disease risk. The G allele of rs7173321 and particularly its homozygous GG genotype are associated with an increased breast cancer risk. Two of the TRPM7 SNPs (rs8042919 and rs7173321) are associated with breast cancer patients in Han Population of Northeast China.
Breast cancer; TRPM7; Genetics
The atmospheric CO2 concentration increases every year. While the effects of elevated CO2 on plant growth, physiology and metabolism have been studied, there is now a pressing need to understand the molecular mechanisms of how plants will respond to future increases in CO2 concentration using genomic techniques.
Gene expression in triploid white poplar ((Populus tomentosa ×P. bolleana) ×P. tomentosa) leaves was investigated using the Affymetrix poplar genome gene chip, after three months of growth in controlled environment chambers under three CO2 concentrations. Our physiological findings showed the growth, assessed as stem diameter, was significantly increased, and the net photosynthetic rate was decreased in elevated CO2 concentrations. The concentrations of four major endogenous hormones appeared to actively promote plant development. Leaf tissues under elevated CO2 concentrations had 5,127 genes with different expression patterns in comparison to leaves under the ambient CO2 concentration. Among these, 8 genes were finally selected for further investigation by using randomized variance model corrective ANOVA analysis, dynamic gene expression profiling, gene network construction, and quantitative real-time PCR validation. Among the 8 genes in the network, aldehyde dehydrogenase and pyruvate kinase were situated in the core and had interconnections with other genes.
Under elevated CO2 concentrations, 8 significantly changed key genes involved in metabolism and responding to stimulus of external environment were identified. These genes play crucial roles in the signal transduction network and show strong correlations with elevated CO2 exposure. This study provides several target genes, further investigation of which could provide an initial step for better understanding the molecular mechanisms of plant acclimation and evolution in future rising CO2 concentrations.
MicroRNAs (miRNAs) are a class of small noncoding RNAs that can regulate gene expression by binding to target mRNAs and induce translation repression or RNA degradation.
There have been many studies indicating that both miRNAs and mRNAs display aberrant expression in breast cancer.
Previously, most researches into the molecular mechanism of breast cancer examined miRNA expression patterns and mRNA expression patterns separately.
In this study, we systematically analysed miRNA-mRNA paired variations (MMPVs),
which are miRNA-mRNA pairs whose pattern of regulation can vary in association with biopathological features, such as the oestrogen receptor (ER),
TP53 and human epidermal growth factor receptor 2 (HER2) genes, survival time, and breast cancer subtypes.
We demonstrated that the existence of MMPVs is general and widespread but that there is a general unbalance in the distribution of MMPVs among the different biopathological features.
Furthermore, based on studying MMPVs that are related to multiple biopathological features, we propose a potential crosstalk mechanism between ER and HER2.
Vast amounts of allergen sequence data have been accumulated, thus complicating the identification of specific allergenic proteins when performing diagnostic allergy tests and immunotherapy. This study aims to rank the importance/potency of the allergens so as to logically reduce the number of allergens and/or allergenic sources. Meta-analysis of 62 allergenic sources used for intradermal testing on 3,335 allergic patients demonstrated that in southern China, mite, sesame, spiny amaranth, Pseudomonas aeruginosa, and house dust account for 88.0% to 100% of the observed positive reactions to the 62 types of allergenic sources tested. The Kolmogorov-Smironov Test results of the website-obtained allergen data and allergen family featured peptides suggested that allergen research in laboratories worldwide has been conducted in parallel on many of the same species. The major allergens were reduced to 21 representative allergens, which were further divided into seven structural classes, each of which contains similar structural components. This study therefore has condensed numerous allergenic sources and major allergens into fewer major representative ones, thus allowing for the use of a smaller number of allergens when conducting comprehensive allergen testing and immunotherapy treatments.
No recent studies have analyzed the rates of or reasons for unanticipated revision surgery within 30 days of primary surgery in spinal deformity patients. Our aim was to examine the incidence, characteristics, reasons, and risk factors for unplanned revision surgery in spinal deformity patients treated at one institution. All patients with a diagnosis of spinal deformity presenting for primary instrumented spinal fusion at a single institution from 1998 to 2012 were reviewed. All unplanned reoperations performed within 30 days after primary surgery were analyzed in terms of demographics, surgical data, and complications. Statistical analyses were performed to obtain correlations and risk factors for anticipated revision. Of 2758 patients [aged 16.07 years (range, 2–71), 69.8% female] who underwent spinal fusion surgery, 59 (2.1%) required reoperation within 30 days after primary surgery. The length of follow up for each patient was more than 30 days. Of those that required reoperation, 87.0% had posterior surgery only, 5.7% had anterior surgery, and 7.3% underwent an anteroposterior approach. The reasons for reoperation included implant failure (n = 20), wound infection (n = 12), neurologic deficit (n = 9), pulmonary complications (n = 17), and coronal plane imbalance (n = 1). The risk factors for reoperation were age, diagnosis, and surgical procedure with osteotomy.
Six candidate height-diameter models were used to analyze the height-diameter relationships. The common methods for estimating the height-diameter models have taken the classical (frequentist) approach based on the frequency interpretation of probability, for example, the nonlinear least squares method (NLS) and the maximum likelihood method (ML). The Bayesian method has an exclusive advantage compared with classical method that the parameters to be estimated are regarded as random variables. In this study, the classical and Bayesian methods were used to estimate six height-diameter models, respectively. Both the classical method and Bayesian method showed that the Weibull model was the “best” model using data1. In addition, based on the Weibull model, data2 was used for comparing Bayesian method with informative priors with uninformative priors and classical method. The results showed that the improvement in prediction accuracy with Bayesian method led to narrower confidence bands of predicted value in comparison to that for the classical method, and the credible bands of parameters with informative priors were also narrower than uninformative priors and classical method. The estimated posterior distributions for parameters can be set as new priors in estimating the parameters using data2.
Until now there have been many reports on hemivertebra resection. But there were no large series on the posterior hemivertebra resection with bisegmental fusion. This is a retrospective study to evaluate the surgical outcomes of posterior hemivertebra resection only with bisegmental fusion for congenital scoliosis caused by fully segmented non-incarcerated hemivertebra.
In our study, 36 consecutive cases (19 males, 17 females) diagnosed with congenital scoliosis, resulting from fully segmented non-incarcerated hemivertebra, treated by posterior hemivertebra resection with bisegmental fusion were investigated retrospectively, with at least a 3 year follow-up period (36–106 months).
The total number of resected hemivertebra was 36. Mean operation time was 188.6 min with average blood loss of 364.2 ml. The segmental scoliosis was corrected from 36.6° to 5.1° with a correction rate of 86.1 %, and segmental kyphosis(difference to normal segmental alignment) from 21.2° to 5.8° at the latest follow-up. The correction rate of the compensatory cranial and caudal curve is 76.4 and 75.1 %. Unanticipated surgeries were performed on eight patients, including one delayed wound healing, two pedicle fractures, one progressive deformity and four implants removals.
Posterior hemivertebra resection with bisegmental fusion allows for early intervention in very young children. Excellent correction can be obtained while the growth potential of the unaffected spine could be preserved well. However, it is not indicated for the hemivertebra between L5 and S1. The most common complication of this procedure is implant failure. Furthermore, in the very young children we noted that although solid fusion could be observed in the fusion level, implants migration may still happen during the time of adolescence, when the height of the body developed rapidly. So a close follow-up is necessary.
Posterior instrumentation; Bisegmetal fusion; Hemivertebra
Urbanizing rural areas in China face a rapidly growing cardiovascular disease burden. Epidemiologic studies and effective preventive strategies are urgently needed.
The Fangshan Cohort Study is a prospective study that began in 2008 and targets local residents aged 40 years or older living in 3 towns in the Fangshan district of Beijing. The baseline examination included a questionnaire on medical history, health knowledge, and behaviors related to cardiovascular disease, as well as physical and blood biochemical examinations. The questionnaire survey will be readministered every 2 years. A system for surveillance of mortality and morbidity of cardiovascular disease is under development.
A total of 20 115 adults (6710 men and 13 405 women) were investigated at baseline (participation rate = 84.5%). The data indicate that overweight/obesity is a serious public health issue in Fangshan: average body mass index was 25.4 kg/m2 among men and 26.5 kg/m2 among women, and the prevalences of overweight and obesity were 43.6% and 10.3% among men and 47.0% and 17.7% among women.
The Fangshan Cohort Study will provide data on cardiovascular risk factors and disease profile, which will assist in developing appropriate prevention and control strategies for cardiovascular disease in rural Chinese communities.
risk factors; cardiovascular disease; rural population; cohort study; China
Soil salt crusts are special layers at soil surface which are widely distributed in the Trim Desert Highway Shelterbelt under drip-irrigation with high salinity groundwater. In order to reveal annual variation of their chemical characteristics, soil salt crusts in shelterbelt of different ages in hinterland of the Taklimakan Desert were sampled. SOM, total salt, inions and pH were analyzed. Following results were obtained. SOM of salt crusts increased with the shelterbelt ages, but increasing trend became lower gradually. Total salt, ions, and pH of salt crusts reduced gradually with the shelterbelt ages. Total salt of salt crusts in shelterbelt of different ages was much higher than shifting sandy land. Ions were higher than shifting sandy land, Cl-, Na+, and SO42- increased more obvious, then Mg2+, K+, Ca2+ and HCO3-, CO32- was little and nearly had no change. pH was all alkaline, pH of salt crusts in shelterbelt of 11 years was even lower than shifting sandy land. We can include that the quality of shallow soil (0~30 cm) in the Trim Desert Highway Shelterbelt becomes better gradually.
Chemical characteristics; Soil salt crusts; Saline groundwater drip-irrigation; Trim Desert Highway Shelterbelt
Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia.
Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) is the most important conifer species for timber production with huge distribution area in southern China. Accurate estimation of biomass is required for accounting and monitoring Chinese forest carbon stocking. In the study, allometric equation was used to analyze tree biomass of Chinese fir. The common methods for estimating allometric model have taken the classical approach based on the frequency interpretation of probability. However, many different biotic and abiotic factors introduce variability in Chinese fir biomass model, suggesting that parameters of biomass model are better represented by probability distributions rather than fixed values as classical method. To deal with the problem, Bayesian method was used for estimating Chinese fir biomass model. In the Bayesian framework, two priors were introduced: non-informative priors and informative priors. For informative priors, 32 biomass equations of Chinese fir were collected from published literature in the paper. The parameter distributions from published literature were regarded as prior distributions in Bayesian model for estimating Chinese fir biomass. Therefore, the Bayesian method with informative priors was better than non-informative priors and classical method, which provides a reasonable method for estimating Chinese fir biomass.
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is a potential remedial therapy for drug craving and relapse, but the mechanism is poorly understood. We investigated changes in neurotransmitter levels during high frequency stimulation (HFS) of the unilateral NAc on morphine-induced rats. Sixty adult Wistar rats were randomized into five groups: the control group (administration of saline), the morphine-only group (systematic administration of morphine without electrode implantation), the morphine-sham-stimulation group (systematic administration of morphine with electrode implantation but not given stimulation), the morphine-stimulation group (systematic administration of morphine with electrode implantation and stimulation) and the saline-stimulation group (administration of saline with electrode implantation and stimulation). The stimulation electrode was stereotaxically implanted into the core of unilateral NAc and microdialysis probes were unilaterally lowered into the ipsilateral ventral tegmental area (VTA), NAc, and ventral pallidum (VP). Samples from microdialysis probes in the ipsilateral VTA, NAc, and VP were analyzed for glutamate (Glu) and γ-aminobutyric acid (GABA) by high-performance liquid chromatography (HPLC). The levels of Glu were increased in the ipsilateral NAc and VP of morphine-only group versus control group, whereas Glu levels were not significantly changed in the ipsilateral VTA. Furthermore, the levels of GABA decreased significantly in the ipsilateral NAc, VP, and VTA of morphine-only group when compared with control group. The profiles of increased Glu and reduced GABA in morphine-induced rats suggest that the presence of increased excitatory neurotransmission in these brain regions. The concentrations of the Glu significantly decreased while the levels of GABA increased in ipsilateral VTA, NAc, and VP in the morphine-stimulation group compared with the morphine-only group. No significant changes were seen in the morphine-sham stimulation group compared with the morphine-only group. These findings indicated that unilateral NAc stimulation inhibits the morphine-induced rats associated hyperactivation of excitatory neurotransmission in the mesocorticolimbic reward circuit.
The cancer stem cell (CSC) theory hypothesizes that CSCs are the cause of tumor formation, recurrence and metastasis. Key to the study of CSCs is their isolation and identification. The present study investigated whether spheroid body-forming cells in the human gastric cancer (GC) MKN-45 cell line are enriched for CSC properties, and also assessed the expression of the candidate CSC markers, octamer-binding transcription factor-4 (OCT4) and adenosine triphosphate-binding cassette transporter G2 (ABCG2) in the MKN-45 spheroid body cells. The MKN-45 cells were plated in a stem cell-conditioned culture system to allow for spheroid body formation. The expression levels of OCT4 and ABCG2 in the spheroid body cells were assessed by qPCR, western blot analysis and immunofluorescence staining, while the tumorigenicity of the spheroid body-forming cells was assessed by in vivo xenograft studies in nude mice. The MKN-45 cells were able to form spheroid bodies when cultured in stem cell-conditioned medium. The spheroid body-forming cells showed a significantly higher (P<0.01) expression of OCT4 and ABCG2 compared with the parental cells. These data suggest that the spheroid body cells from the MKN-45 GC cell line cultured in stem cell-conditioned medium possessed gastric CSC properties. The co-expression of OCT4 and ABCG2 by these cells may represent the presence of a subpopulation of gastric CSCs.
human gastric cancer; cancer stem cell; OCT4; ABCG2
In this study, a five-generation Chinese family (family F013) with progressive autosomal dominant hearing loss was mapped to a critical region spanning 28.54 Mb on chromosome 9q31.3-q34.3 by linkage analysis, which was a novel DFNA locus, assigned as DFNA56. In this interval, there were 398 annotated genes. Then, whole exome sequencing was applied in three patients and one normal individual from this family. Six single nucleotide variants and two indels were found co-segregated with the phenotypes. Then using mass spectrum (Sequenom, Inc.) to rank the eight sites, we found only the TNC gene be co-segregated with hearing loss in 53 subjects of F013. And this missense mutation (c.5317G>A, p.V1773M ) of TNC located exactly in the critical linked interval. Further screening to the coding region of this gene in 587 subjects with nonsyndromic hearing loss (NSHL) found a second missense mutation, c.5368A>T (p. T1796S), co-segregating with phenotype in the other family. These two mutations located in the conserved region of TNC and were absent in the 387 normal hearing individuals of matched geographical ancestry. Functional effects of the two mutations were predicted using SIFT and both mutations were deleterious. All these results supported that TNC may be the causal gene for the hearing loss inherited in these families. TNC encodes tenascin-C, a member of the extracellular matrix (ECM), is present in the basilar membrane (BM), and the osseous spiral lamina of the cochlea. It plays an important role in cochlear development. The up-regulated expression of TNC gene in tissue repair and neural regeneration was seen in human and zebrafish, and in sensory receptor recovery in the vestibular organ after ototoxic injury in birds. Then the absence of normal tenascin-C was supposed to cause irreversible injuries in cochlea and caused hearing loss.
The goal of this study was to identify mutations in 25 known causative genes in 47 unrelated Chinese families with cone-rod dystrophy (CORD).
Forty-seven probands from unrelated families with CORD were recruited. Genomic DNA prepared from leukocytes was analyzed by whole exome sequencing. Variants in the 25 genes were selected and then validated by Sanger sequencing.
Fourteen potential pathogenic mutations, including nine novel and five known, were identified in 10 of the 47 families (21.28%). Homozygous, compound heterozygous, and hemizygous mutations were detected in three, four, or three families, respectively. The 14 mutations in the 10 families were distributed among CNGB3 (three families), PDE6C (two families), ABCA4 (one family), RPGRIP1 (one family), RPGR (two families), and CACNA1F (one family).
This study provides a brief view on mutation spectrum of the 25 genes in a Chinese cohort with CORD. Identification of novel mutations enriched our understanding of variations in these genes and their associated phenotypes. To our knowledge, this is the first systemic exome-sequencing analysis of all of the 25 CORD-associated genes.
Chest radiologists rely on the segmentation and quantificational analysis of ground-glass opacities (GGO) to perform imaging diagnoses that evaluate the disease severity or recovery stages of diffuse parenchymal lung diseases. However, it is computationally difficult to segment and analyze patterns of GGO while compared with other lung diseases, since GGO usually do not have clear boundaries. In this paper, we present a new approach which automatically segments GGO in lung computed tomography (CT) images using algorithms derived from Markov random field theory. Further, we systematically evaluate the performance of the algorithms in segmenting GGO in lung CT images under different situations. CT image studies from 41 patients with diffuse lung diseases were enrolled in this research. The local distributions were modeled with both simple and adaptive (AMAP) models of maximum a posteriori (MAP). For best segmentation, we used the simulated annealing algorithm with a Gibbs sampler to solve the combinatorial optimization problem of MAP estimators, and we applied a knowledge-guided strategy to reduce false positive regions. We achieved AMAP-based GGO segmentation results of 86.94%, 94.33%, and 94.06% in average sensitivity, specificity, and accuracy, respectively, and we evaluated the performance using radiologists’ subjective evaluation and quantificational analysis and diagnosis. We also compared the results of AMAP-based GGO segmentation with those of support vector machine-based methods, and we discuss the reliability and other issues of AMAP-based GGO segmentation. Our research results demonstrate the acceptability and usefulness of AMAP-based GGO segmentation for assisting radiologists in detecting GGO in high-resolution CT diagnostic procedures.
Image segmentation; Lung diseases; Markov chains; Tomography; X-ray computed
Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.
Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.
The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.
These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.
Olmsted syndrome; TRPV3; IgE; Eosinophil; Follicular T cell