目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分...目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分析候选致病基因的组织表达特点和生物学功能。构建致病基因野生型以及变异型蛋白三维结构,利用Gromacs软件对野生型和变异型蛋白进行分子动力学模拟。检索ClinVar数据库分析已报道致病和可能致病性变异在蛋白结构域分布。结果孕妇有DWM妊娠史。胎儿在孕22周开始出现DWM相关症状。胎儿羊水染色体核型分析以及CNV-seq检测未见异常。全外显子测序结果显示,胎儿携带纤维蛋白溶酶原(plasminogen,PLG)复合杂合变异:c.2251G>A(p.G751R)和c.1781G>A(p.W594*)。这两个可能致病性变异分别遗传自父亲、母亲,且均位于PLG的Peptidase S1结构域,c.1781G>A(p.W594*)未见报道。c.2251G>A(p.G751R)可以影响PLG蛋白的RMSD、RMSF以及回旋半径,进而影响蛋白生物功能。结论PLG基因2251G>A(p.G751R)和c.1781G>A(p.W594*)复合杂合变异是导致DWM的病因。展开更多
目的:本研究旨在探讨NT联合NIPT、早期唐氏筛查及四维超声检查在胎儿染色体疾病筛查中的临床应用价值,评估不同检测方法单独及联合使用时的检出率和诊断效能,为优化胎儿染色体异常的早期筛查策略提供依据。方法:回顾性分析2018年1月至2...目的:本研究旨在探讨NT联合NIPT、早期唐氏筛查及四维超声检查在胎儿染色体疾病筛查中的临床应用价值,评估不同检测方法单独及联合使用时的检出率和诊断效能,为优化胎儿染色体异常的早期筛查策略提供依据。方法:回顾性分析2018年1月至2024年10月于青海红十字医院行产前诊断的532例孕妇的临床数据,所有病例均行NT、NIPT、早期唐氏筛查、四维超声检查及羊水穿刺。分别计算各检测方法单独及联合筛查的阳性检出率、灵敏度、特异度、阳性预测值、阴性预测值及准确率,同时对多种检测联合方案的诊断效能进行ROC曲线分析。结果:两组孕妇的年龄、孕周、孕前BMI、居住地与文化程度均无统计学差异(P > 0.05)。单独检测中,相比NT、早期唐氏筛查及四维超声检查,NIPT具有较高的阳性检出率、灵敏度、特异度、阳性预测值、阴性预测值、准确率及AUC (P Objective: The aim of this study was to investigate the clinical application value of NT combined with NIPT, early Down’s screening, and four-dimensional ultrasonography in the screening of fetal chromosomal disorders, to assess the detection rate and diagnostic efficacy of different testing methods when used individually and in combination, and to provide a basis for optimising the early screening strategy for fetal chromosomal abnormalities. Methods: Clinical data of 532 pregnant women who underwent prenatal diagnosis in Qinghai Red Cross Hospital from January 2018 to October 2024 were retrospectively analysed, and all cases underwent NT, NIPT, early Down’s syndrome screening, four-dimensional ultrasonography, and amniocentesis. The positive detection rate, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each test alone and in combination were calculated, and the diagnostic efficacy of the combination of multiple tests was analysed by ROC curve. Results: There were no statistically significant differences in age, gestational week, pre-pregnancy BMI, place of residence, and education between the two groups (P > 0.05). Among individual tests, compared with NT, early Down’s screening, and 4D ultrasound, NIPT alone had a higher positive detection rate, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and AUC (P < 0.05). Compared to individual screening, NT combined with early Down syndrome screening, and NT combined with four dimensional ultrasound examination, NT combined with NIPT had higher sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and AUC (P < 0.05). Conclusion: NT combined with NIPT, early Down’s syndrome screening, and four-dimensional ultrasound can significantly improve the detection rate and diagnostic accuracy of individual screening, especially the combined NT + NIPT program has high clinical value in the screening of fetal chromosomal abnormalities, which provides a scientific basis for optimizing the screening strategy for high-risk pregnant women.展开更多
文摘目的分析1例Dandy-Walker综合征(DWM)的遗传学病因。方法收集胎儿B超、MRI、出生后症状、染色体核型分析、CNV-seq检查以及WES测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、STRING数据库,分析候选致病基因的组织表达特点和生物学功能。构建致病基因野生型以及变异型蛋白三维结构,利用Gromacs软件对野生型和变异型蛋白进行分子动力学模拟。检索ClinVar数据库分析已报道致病和可能致病性变异在蛋白结构域分布。结果孕妇有DWM妊娠史。胎儿在孕22周开始出现DWM相关症状。胎儿羊水染色体核型分析以及CNV-seq检测未见异常。全外显子测序结果显示,胎儿携带纤维蛋白溶酶原(plasminogen,PLG)复合杂合变异:c.2251G>A(p.G751R)和c.1781G>A(p.W594*)。这两个可能致病性变异分别遗传自父亲、母亲,且均位于PLG的Peptidase S1结构域,c.1781G>A(p.W594*)未见报道。c.2251G>A(p.G751R)可以影响PLG蛋白的RMSD、RMSF以及回旋半径,进而影响蛋白生物功能。结论PLG基因2251G>A(p.G751R)和c.1781G>A(p.W594*)复合杂合变异是导致DWM的病因。
文摘目的:本研究旨在探讨NT联合NIPT、早期唐氏筛查及四维超声检查在胎儿染色体疾病筛查中的临床应用价值,评估不同检测方法单独及联合使用时的检出率和诊断效能,为优化胎儿染色体异常的早期筛查策略提供依据。方法:回顾性分析2018年1月至2024年10月于青海红十字医院行产前诊断的532例孕妇的临床数据,所有病例均行NT、NIPT、早期唐氏筛查、四维超声检查及羊水穿刺。分别计算各检测方法单独及联合筛查的阳性检出率、灵敏度、特异度、阳性预测值、阴性预测值及准确率,同时对多种检测联合方案的诊断效能进行ROC曲线分析。结果:两组孕妇的年龄、孕周、孕前BMI、居住地与文化程度均无统计学差异(P > 0.05)。单独检测中,相比NT、早期唐氏筛查及四维超声检查,NIPT具有较高的阳性检出率、灵敏度、特异度、阳性预测值、阴性预测值、准确率及AUC (P Objective: The aim of this study was to investigate the clinical application value of NT combined with NIPT, early Down’s screening, and four-dimensional ultrasonography in the screening of fetal chromosomal disorders, to assess the detection rate and diagnostic efficacy of different testing methods when used individually and in combination, and to provide a basis for optimising the early screening strategy for fetal chromosomal abnormalities. Methods: Clinical data of 532 pregnant women who underwent prenatal diagnosis in Qinghai Red Cross Hospital from January 2018 to October 2024 were retrospectively analysed, and all cases underwent NT, NIPT, early Down’s syndrome screening, four-dimensional ultrasonography, and amniocentesis. The positive detection rate, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each test alone and in combination were calculated, and the diagnostic efficacy of the combination of multiple tests was analysed by ROC curve. Results: There were no statistically significant differences in age, gestational week, pre-pregnancy BMI, place of residence, and education between the two groups (P > 0.05). Among individual tests, compared with NT, early Down’s screening, and 4D ultrasound, NIPT alone had a higher positive detection rate, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and AUC (P < 0.05). Compared to individual screening, NT combined with early Down syndrome screening, and NT combined with four dimensional ultrasound examination, NT combined with NIPT had higher sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and AUC (P < 0.05). Conclusion: NT combined with NIPT, early Down’s syndrome screening, and four-dimensional ultrasound can significantly improve the detection rate and diagnostic accuracy of individual screening, especially the combined NT + NIPT program has high clinical value in the screening of fetal chromosomal abnormalities, which provides a scientific basis for optimizing the screening strategy for high-risk pregnant women.
