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Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.
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Objective:To investigate the predictive value of different body obesity measures for non-alcoholic fatty liver disease (NAFLD).Methods:It was a cross-sectional study. The present study was a case-control study involving 553 subjects who underwent physical examination from January to April 2022. The subjects were divided into NAFLD group ( n=321 cases) and control group ( n=232 cases) according to abdominal ultrasound imaging parameters. All subjects completed a general information questionnaire, liver ultrasound examination, serum biochemical indices and physical measurements. Logistic regression model was used to analyze the correlation between human obesity measures (neck circumference, triceps skinfold thickness (TSF),body mass index (BMI), waist-to-hip ratio, lipid accumulation index (LAP), visceral fat index (VAI), body roundness index (BRI) and a body shape index (ABSI)) and NAFLD. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of single and combined measures of obesity for NAFLD. Results:The subjects were stratified by gender, and the quartile levels of BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI were all correlated with NAFLD in both male and female (all P<0.05). After further adjustment for confounding factors, compared with those in group Q 1, group Q 4 of the above-mentioned indexes still had higher odds ratios ( P<0.05). The AUC value of LAP in predicting NAFLD was the largest in both men and women, which was 0.836(0.788-0.876) and 0.885(0.839-0.921), and the cut-off value was 41.93 and 33.27, respectively. There was no significant difference in AUC of ROC predicting NAFLD among LAP, BRI and BMI ( P>0.05). The AUC of ABSI in predicting NAFLD was less than 0.7(namely 0.584(0.525-0.641) and 0.679(0.618-0.735) in men and women, respectively), which indicated poor predictive performance for NAFLD. In the pairwise combination index, the AUC of ROC predicting NAFLD with TSF+LAP in male was the largest, which was 0.864(0.819-0.901), and there was statistical significance when compared with BRI (AUC=0.818(0.769-0.860)) and BMI (AUC=0.816(0.767-0.858)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.836(0.788-0.876)) ( P>0.05). The AUC of ROC predicting NAFLD with VAI+LAP in women was the largest, it was 0.894(0.849-0.928), there was statistical significance when compared with BMI (AUC=0.849(0.799-0.890)) ( P<0.05), but there was no statistical significance when compared with LAP (AUC=0.885(0.839-0.921)) and BRI (AUC=0.870(0.822-0.908)) ( P>0.05). Conclusion:BMI, neck circumference, TSF, waist-to-hip ratio, LAP, VAI and BRI all have good predictive value for NAFLD.
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Objective To analyze the electroencephalograph (EEG) features of 43 patients with clinically possible or probable Creutzfeldt-Jakob disease (CJD) and its correlation with megnetic resonance imaging (MRI) imaging and clinical manifestations.Methods All patients diagnosed with suspected CJD who were hospitalized in Xuanwu Hospital from January 2013 to December 2015 were collected.The clinical data, EEG and MRI imaging features were analyzed retrospectively.Based on the periodic sharp wave complexes (PSWC) appearance in EEG results, the patients were divided into typically changed group (TCG), atypically changed group (ACG) and unchanged group (UCG).Age, disease duration, clinical manifestations and MRI features among three groups were analyzed and the correlations between patient′s EEG features and age, disease duration, clinical manifestations or MRI features were explored using spearman method.Results Among the 43 patients with possible or probable CJD disease, 26 were male and 17 were female with an average disease duration of 4 months.The age of onset ranged from 31 to 80 with an average of (58.0±9.8) years old, and 86.0% of patients were 51 years old or above.Clinical characteristics of CJD patients according to occurrence rate were as follows: 35 cases (81.4%) with cognitive impairment, 29 cases (67.4%) with mental and behavior disorder, 28 cases (65.1%) with pyramidal tract damage, 24 cases (55.8%) with cerebellar symptoms, 23 cases (53.5%) with extrapyramidal symptoms,17 cases (39.5%) with myoclonic, 13 cases (30.2%) with dyssomnia, 13 cases (30.2%) with visual disorder and 2 cases (4.7%) with akinetic mutism.Regarding EEG features, 39.53% (17/43) of patients showed typical periodic sharp wave complexes (PSWC) (TCG group), 51.2% (22/43) had irregular rhythm and different forms of slow wave (ACG group) and only 9.3% (4/43) had no EEG change (UCG group).The occurrence rate of ribbon sign in MRI was 82.4% (14/17) in TCG group, 77.3% (17/22) in ACG group and none in UCG group.The rates were significantly higher in TCG and ACG group than that in UCG group (both P0.05).Conclusions EEG showed typical changes associated with disease duration in different stages of disease.EEG and MRI are two different means to evaluate different aspects of patients with CJD disease, and combination of two means could achieve better evaluation results.