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1.
Physiol Res ; 70(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33453721

RESUMO

The pathogenesis of hepatic encephalopathy (HE) has been generally linked to blood ammonia, gamma-aminobutyric acid and serotonin. However, the exact mechanism remains unclear. In the present study, we aimed to explore the role of hippocampal dopamine (DA) and its receptors in the pathogenesis of HE through the use of behavioral testing, western blotting, and immunofluorescence staining in normal rats, HE model rats and rats treated with the DA precursor-levodopa (L-DOPA). HE model rats manifested fibrotic livers and showed serious behavioral disorders. They also had significantly lower hippocampal DA content and increased expression of both D1 and D2 receptors relative to normal rats. After treatment with L-DOPA, the HE model rats showed normal behavior and expression of D1 returned to normal levels. Furthermore, pretreatment with the D1 antagonist SCH23390 blocked the therapeutic effect of L-DOPA on behavior in HE model rats. Taken together, these results clarify that the decrease in hippocampal DA plays a role in the pathogenesis of HE and that this effect is mediated by D1. These findings provide new evidence for the pathogenesis of HE.

2.
Eur J Neurol ; 28(2): 491-499, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32961598

RESUMO

BACKGROUND AND PURPOSE: To estimate health-related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)]. METHODS: We performed a cross-sectional observational study on patients with CCMs admitted to our department from 1 November 2017 to 10 January 2020 using standardized interviews [short-form-36 questionnaire, hospital anxiety and depression score (HADS-A/D), CCM perception questionnaire]. Included criteria were diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. Health-related quality of life (HRQOL) data were analyzed and compared to the German normal population. Uni- and multivariate analyses were carried out to identify variables with impact on outcome. RESULTS: Two hundred nineteen (93%) of 229 eligible patients were included. Mean age was 46.3 ± 14.7 (18-86) years; 136 (62%) were female. Ninety-eight (45%) patients presented with symptomatic hemorrhage (SH), and 17 (8%) with repetitive SH. Ninety-two (42%) patients were asymptomatic. Thirty-seven patients (17%) suffered from cavernoma-related epilepsy. Twenty-eight patients (13%) suffered from familial CCMs. Patients showed significantly decreased component scores and subdomain scores compared to the normal population, with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS-A was significantly increased. HADS-A/D strongly correlated with mental component score and individual perception of the CCM. CONCLUSIONS: Patients with the diagnosis of a CCM showed decreased HRQOL compared to the normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmarks in evaluation of different (future) management strategies.

3.
Clin Radiol ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33272531

RESUMO

AIM: To assess the potential of texture analysis (TA) applied in T1 maps and extracellular volume (ECV) obtained using cardiac magnetic resonance (CMR) in the diagnosis of hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) compared with normal controls (NC). Strain parameters were analysed to compare with final TA models. MATERIALS AND METHODS: This retrospective study included 66 HCM patients, 39 HHD patients, and 41 NC. Step-wise dimension reduction and feature selection were performed by reproducibility, machine learning, collinearity, and multivariable regression analysis to select the texture features that enable diagnosis of and differentiation between HCM and HHD. Strain parameters were calculated by short-axis and three long-axis cine sequences. RESULTS: Independent features in T1 maps and ECV analysis allowed for the differentiation between patients (HCM and HHD) and NC. Of the best-calculated model, the areas under the receiver operating curve (AUCs) were as follows: 0.969 for T1 map and 0.964 for ECV. To distinguish HCM from HHD, two independent features were screened out for both T1 and ECV maps. The AUCs were as follows: 0.793 for T1 map and 0.894 for ECV. Radial, circumferential, and longitudinal strain parameters could differentiate patients from NC, but only longitudinal strain parameters was significantly different between HCM and HHD. CONCLUSIONS: Texture analysis of T1 maps and ECV shows high accuracy in differentiating hypertrophic myocardium from NC, and HCM from HHD. Strain parameters are able to demonstrate the difference between patients and NC, but were less impressive in differentiating HCM and HHD.

5.
Zhonghua Yi Xue Za Zhi ; 100(46): 3694-3701, 2020 Dec 15.
Artigo em Chinês | MEDLINE | ID: mdl-33342147

RESUMO

Objective: To study the expression and clinical significance of calcineurin B homologous protein 2 (CHP2) in gastric cancer (GC) and its effect on malignant phenotype of GC cells. Methods: The protein expression of CHP2 in 297 GC tissue and 198 normal gastric tissue samples were detected by immunohistochemistry. The relationship between the expression of CHP2 and clinicopathologic parameters of GC were analyzed. CHP2-overexpression plasmids and CHP2-interference plasmids were transfected into GC cell lines respectively. Wound healing assay and Transwell experiment was used to detect the invasion and migration ability of GC cells, and cell counting kit-8 (CCK-8) method was used to detect the proliferation ability of GC cells. Results: The positive expression rate of CHP2 in GC was 68.7% (204/297), which was higher in benign margin (34.1%) (31/91), chronic gastritis (59.1%) (13/22), intestinal metaplasia (34.2%) (13/38), low-grade intraepithelial neoplasia (40.0%) (12/30) and high-grade intraepithelial neoplasia (41.2%)(7/17). The positive expression of CHP2 was correlated with tumor, node and metastasis (TNM) stage, lymph node metastasis and distant metastasis (all P<0.05), but not with gender, age, Laurén classification, human epidermal growth factor receptor 2 (HER2) levels, depth of invasion, carcinoembryonic antigen (CEA) level and CEA 19-9 level (all P>0.05). The results of multivariate analysis showed that high expression of CHP2 and TNM stage were both independent parameters for predicting GC patient prognosis (both P<0.05). Interference of CHP2 expression in HGC-27 cells suppressed proliferation and migration significantly (P<0.05). However, over-expression CHP2 in AGS cells promoted proliferation, and migration significantly (P<0.05). Conclusion: CHP2 plays an important role in the development of GC, which is expected to be a molecular marker for patient prognosis and a potential target of targeted therapy for GC patients.


Assuntos
Calcineurina , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Fenótipo , Prognóstico
7.
Artigo em Inglês | MEDLINE | ID: mdl-33242601

RESUMO

OBJECTIVE: Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. METHODS: Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by CCK-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. RESULTS: In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1ß-treated NPCs. Mechanistically, QUE suppressed IL-1ß induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. CONCLUSIONS: Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

8.
Br J Dermatol ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236347

RESUMO

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

9.
Zhonghua Yi Xue Za Zhi ; 100(43): 3419-3424, 2020 Nov 24.
Artigo em Chinês | MEDLINE | ID: mdl-33238672

RESUMO

Objective: To investigate the severity of stress, anxiety, depression and insomnia during the novel coronavirus disease (COVID-19) pandemic in adults outside Hubei Province, China. Methods: An online survey of psychological and sleep by using Questionnaire Star program from 5th to 19th February 2020 was conducted. The Impact of Event Scale-Revised was used to assess COVID-19 outbreak-related stress symptoms. Meanwhile, Questionnaires of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9 and the Insomnia Severity Index were respectively used to assess the severity of anxiety, depression and insomnia symptoms prior to and during the COVID-19 pandemic. Results: A total of 3 134 subjects were included. Among the included subjects, 15.5% (487), 24.9% (779), 28.7% (899) and 30.9% (968) of the subjects had COVID-19-related stress symptoms, anxiety, depression and insomnia after the COVID-19 outbreak, respectively. The severity levels of anxiety, depression and insomnia were significantly increased during the COVID-19 pandemic compared to prior to the outbreak (all P<0.01). Furthermore, the subjects' stress response to the COVID-19 outbreak was an independent risk factor for increased anxiety, depression and insomnia after the outbreak. Conclusion: The COVID-19 outbreak resulted in related stress response and widespread increase in anxiety, depression, and insomnia outside Hubei Province, China in the general population. The aggravation of anxiety, depression and insomnia is associated with stress levels. Our data demonstrate that the widespread psychological and insomnia problems in the general population need to be addressed at the early phase of the pandemic.


Assuntos
Infecções por Coronavirus , Coronavirus , Pandemias , Pneumonia Viral , Distúrbios do Início e da Manutenção do Sono , Adulto , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Betacoronavirus , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Distúrbios do Início e da Manutenção do Sono/epidemiologia
13.
Zhonghua Yi Xue Za Zhi ; 100(39): 3104-3108, 2020 Oct 27.
Artigo em Chinês | MEDLINE | ID: mdl-33105963

RESUMO

Objective: To explore the effect of a delayed pedicle gastrocnemius muscle flap transposition for the treatment of a knee joint deep infection secondary to wound necrosis after total knee arthroplasty (TKA). Methods: The clinical data of 7 patients treated in Shanxi Provincial People's Hospital with a delayed pedicle gastrocnemius muscle flap transposition from December 2015 to September 2019 for wound necrosis, exposed prosthesis and deep infection of knee joint after TKA were analyzed retrospectively. Before the muscle flap transplantation, 5 of the patients had received at least one debridement but failed for relapse, and resulted in an exposed prostheses and infected knee joint. Four patients were positive in their wounds or joint exudates bacterial culture, while the other 3 patients were negative but only with an obvious purulent secretion. The radiographs in all of the patients had no signs of lucent peripheral to or sink of the prosthesis. Results: The patients were followed-up for a mean time of 16.5 months (7-39 months). The flap and skin graft survived uneventfully with no pain, sinus, fistula, edema, and hematoma occurred. The appearances of the legs were normal. Only 1 patient had a mild limp, and the others gained almost a normal gait. One of the patients recurred 5 months after the gastrocnemius muscle flap transposition, and a two-stage revision procedure was applied, that involving a prosthesis remove and vancomycin impregnated cement (4 grams of vancomycin powder mixed with forty grams of polymethylmethacrylate) spacer implanted, and a new prosthesis was re-implanted 6 months later. The assessment of Knee Society Score (KSS) graded as: 4 patients classified as excellence, 2 as fine, 1 as general. Conclusions: Delayed pedicle gastrocnemius muscle flap transposition is an effective method for the complication of wound necrosis, deep infection, prosthesis exposure after TKA. This protocol was appropriate for those who have experienced a comparative long time of infection while had no signs of prosthesis loosening, and with which the implant may be salvaged, the defect be closed, and the infection be eradicated.


Assuntos
Artroplastia do Joelho , Infecções , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Músculo Esquelético , Estudos Retrospectivos
14.
Artigo em Inglês | MEDLINE | ID: mdl-33105994

RESUMO

Tribomagnetization, a natural phenomenon known for decades, has many engineering applications today. However, its intrinsic origin remains controversial and the mechanistic-based model has not yet been developed to predict the tribomagnetization behavior. In this work, the origin of tribomagnetization is investigated via both the experimental and modeling approaches. For the first time, the expansion of surface plastic deformation to the subsurface layer (i.e., dislocation strain gradient) is characterized in conjunction with the tribological behavior of the interface. By performing the reciprocating sliding experiment in a pin-on-block contact configuration, the tribomagnetization evolution in different wear regimes is followed, the geometrically necessary dislocations (GNDs) developed in the subsurface are measured, and the formation of characteristic magnetic domains is revealed. A tribomagnetization model is proposed on the basis of the sliding-induced plastic deformation mechanism with GNDs, bringing the missing link with classical tribology and ferromagnetism. The model reveals that the surface plastic strain and width of a wear scar are two crucial factors in determining the surface magnetic field changes. We believe that the tribomagnetization originates from the magnetic distortion accompanied by the progression of GNDs in the subsurface. Our hypothesis is supported by the good agreement between the model prediction and experimental observation.

15.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(9): 1465-1470, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-33076600

RESUMO

Objective: To explore the relationship between sedentary time and the incidence of type 2 diabetes in adults in China. Methods: Data collected from the Chinese Chronic Disease and Risk Factor Surveillance (CCDRFS) in 2010 were used as baseline data. Eight provinces where CCDRFS were conducted in 2010 were selected, and two surveillance spots (one in urban area and another one in rural area) of each provinces were further selected for the follow-up studies. After excluding diagnosed diabetes patients according to baseline data, a total of 8 625 of subjects were recruited as participants. In the follow up carried out from 2016 to 2017, a total of 5 991 people received complete follow up. Cox proportional hazards models were used to analyze the relationship between sedentary time and the incidence of type 2 diabetes, and subgroup analysis was conducted based on variables such as gender, geographic area, and urban area or rural areas. Results: A total of 5 782 subjects were included in final analysis. During an average 6.4 years of follow up (36 927.0 person-years), 592 participants developed type 2 diabetes, the incidence rate was 16.0 per 1 000 person years. Multivariate Cox regression analysis showed that after adjustment for possible confounders, compared with the 0.0-h/d group, the risk of diabetes incidence increased by 33% (HR=1.33, 95%CI: 1.05-1.68) for those who had sedentary time for more than 6.0 h every day. The subgroup analysis showed that the significant association was only observed in those who were men, current smokers, central obese, had family history of diabetes, had rural residency, and lived in eastern and central areas of China. Conclusions: Longer sedentary time can increase the risk of type 2 diabetes. Lifestyle intervention should be strengthened to reduce sedentary time, especially for people who had sedentary time for more than 6.0 h every day.


Assuntos
Diabetes Mellitus Tipo 2 , Comportamento Sedentário , Adulto , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
16.
Mol Biol (Mosk) ; 54(5): 802-812, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33009790

RESUMO

Non-coding RNAs are a class of RNAs with multiple roles in plant life. Covalently closed circular RNA molecules (circRNAs) have been recently shown to be a group of RNA isoforms that show widespread tissue-specific expression in plants, often cooperating with the corresponding linear mRNAs to regulate gene function. However, no previous study of poplar has identified circRNAs in the cambium and determined their potential roles in the cambium or xylem development. In the present study, we sequenced RNAs in the cambium of poplar seedlings at two developmental stages, and identified and characterized 4912 circRNAs. Alternative back-splicing circularization events for 87 genes were identified among the circRNAs derived from different chromosomes. A total of 1138 circRNAs originated from 928 host genes, which were classified among the three major functional categories by GO analysis. Thirty-nine circRNAs were differentially expressed between cambium samples of stems at two developmental stages. Twenty-four DEcircRNAs interacted with 98 miRNAs as targets, of which some were associated with cambium growth and development. The results suggest that circRNAs play important roles in the cambium in relation to the regulation of stem growth and development in poplar seedlings.


Assuntos
Câmbio/genética , MicroRNAs , Populus/genética , RNA Circular/genética , RNA de Plantas/genética , MicroRNAs/genética , RNA Mensageiro , Plântula/genética
17.
Eur Rev Med Pharmacol Sci ; 24(16): 8439-8446, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32894550

RESUMO

OBJECTIVE: To detect the expression level of long intergenic non-protein coding RNA 1198 (LINC01198) in colorectal cancer (CRC) tissues and cells, to investigate the effect of LINC01198 on the biological function of CRC cells through in vivo and in vitro experiments, and to explore its molecular mechanism. PATIENTS AND METHODS: Tissue samples were collected from 32 patients with CRC. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect the relative expression level of LINC01198 in CRC tissues and cells. In vitro experiments [Cell Counting Kit-8 (CCK-8) and flow cytometry] were conducted to explore the effect of interfering with the expression of LINC01198 on the proliferation, cycle and apoptosis of CRC cells. Tumorigenesis assay was undertaken in nude mice to investigate the influence of LINC01198 on the tumorigenic ability of CRC cells in vivo. Besides, Western blotting was performed to determine the changes in the downstream signaling pathway of LINC01198. RESULTS: Among the 32 cases of tissue samples of CRC patients, 28 cases had an upregulated expression of LINC01198 compared with paracancerous tissues. The results of qRT-PCR indicated that LINC01198 expression was upregulated in CRC cells, and the interference efficiency of si-LINC01198 was measured via qRT-PCR. The results of in vitro experiments demonstrated that after interfering with the expression of LINC01198 in CRC cells, cell proliferation capacity was inhibited, cell cycle was arrested at G1/G0 phase, and the apoptosis rate was increased. The results of nude mice tumorigenesis experiments revealed that after interfering with the expression of LINC01198, the tumorigenic ability of CRC cells in vivo declined. Additionally, Western blotting assay results confirmed that after interfering with the expression of LINC01198, the expression of molecular markers in the Notch signaling pathway was inhibited. CONCLUSIONS: The expression of LINC01198 is upregulated in the case of CRC, which promotes proliferation and inhibits apoptosis of CRC cells by regulating the Notch signaling pathway. Our findings provide a novel biomarker for the diagnosis and treatment of HCC patients and treatment strategies.

18.
Zhonghua Zhong Liu Za Zhi ; 42(8): 653-659, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867457

RESUMO

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P<0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P<0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.


Assuntos
Neoplasias da Mama/patologia , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Nomogramas , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Axila , Humanos , Linfonodos/patologia , Estudos Retrospectivos
19.
Zhonghua Shao Shang Za Zhi ; 36(9): 880-882, 2020 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-32972077

RESUMO

In November 4, 2016, a 1 year and 3 months old male patient with face and neck scald complicated with severe scald of oropharynx was admitted to Guangzhou Red Cross Hospital 1 hour after injury. The child developed upper respiratory tract obstruction 2 hours after injury, therefore tracheotomy and intubation were performed immediately to establish an artificial airway, and symptomatic treatments such as anti-infection, fluid replacement, and dressing change were conducted. On the 10th day after injury, the child had difficult breathing during the test tube blocking before extubation, and it was difficult to extubate. Symptomatic treatments such as ventilator assisted ventilation and strengthened anti-infection were continued. On the 17th day after injury, extubation plan was adjusted. Thirty minutes before extubation, phenobarbital was injected intramuscularly for sedation, and atropine was used to reduce airway secretions, after which extubation was successful. After 21 days of treatment, the child was cured and discharged. In the treatment of this case, high attention was paid to the important influence of children's mental factors among causes of difficult extubation, which provided a reference for clinical treatment of extubation in children with tracheal tube after tracheotomy.


Assuntos
Extubação , Traqueotomia , Humanos , Lactente , Masculino , Orofaringe , Respiração Artificial , Traqueostomia
20.
Artigo em Chinês | MEDLINE | ID: mdl-32911884

RESUMO

Objective: To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing. Methods: The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance. Results: The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions: Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.


Assuntos
Caderinas , Surdez , Perda Auditiva Neurossensorial , Síndromes de Usher , Caderinas/genética , Surdez/genética , Potenciais Evocados Visuais , Éxons , Perda Auditiva Neurossensorial/genética , Humanos , Mutação , Linhagem , Fenótipo , Síndromes de Usher/genética
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