Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies.
Biochemical and genetic approaches to the prenatal diagnosis of propionic acidemia in 78 pregnancies.
复制标题
78 例妊娠丙酸血症产前诊断的生化和遗传学方法
DOI：
10.1186/s13023-020-01539-w
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发表时间：
2020-10-07
影响因子：
3.7
通讯作者：
Han L
中科院分区：
文献类型：
--
作者：
Dai M;Xiao B;Zhang H;Ye J;Qiu W;Zhu H;Wang L;Liang L;Zhan X;Ji W;Wang Y;Yu Y;Gu X;Han L
背景丙酸血症（Propionic Acidemia，PA）是一种严重的代谢性疾病，其产前诊断方法多种多样。评价生化方法产前诊断PA的可靠性和有效性，我们在一个中心进行了11年的回顾性研究。方法我们收集了来自58个家庭的78例孕妇的数据，并通过直接遗传分析和/或使用串联质谱（MS/MS）和气相色谱/质谱（GC/MS）进行代谢物测量来提供产前诊断。结果65例正常胎儿（83.33%）和13例受累胎儿（16.67%）在我们的研究中得到证实。特征代谢产物丙酰肉碱（C3）、C3/乙酰肉碱（C2）比值和2-甲基柠檬酸（2 MCA）水平在正常组和患病组之间存在显著性差异而3-羟基丙酸（3 HPA）水平在两组间无显著性差异（P> 0.05在78例妊娠中，24例胎儿存在一种致病性变异或无先证者遗传信息。其中3只胎仔的C3、C3/C2比值和2 MCA AF水平升高，因此确定受影响，而基于正常AF代谢产物谱，确定其余胎仔未受影响。我们的遗传和生化结果是高度一致的产后随访结果对所有未受影响的fetals.ConclusionsWe的结论是，生化方法可以作为一种快速，方便的产前诊断方法，妊娠在PA的风险增加，可用于与基因检测，这种疾病的精确产前诊断。结果表明，AF细胞培养上清中特征代谢产物C3、C3/C2比值和2 MCA水平是诊断PA的可靠生化指标，其中C3/C2比值是诊断PA最可靠的生化指标。
BackgroundPropionic acidemia (PA) is a serious metabolic disorder, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability and validity of a biochemical strategy in the prenatal diagnosis of PA, we conducted a retrospective study of our 11-year experiences at a single center.MethodsWe accumulated data from 78 pregnancies from 58 families referred to our center and provided prenatal diagnosis by directed genetic analysis and/or metabolite measurement using tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GC/MS) of amniotic fluid (AF) samples.ResultsSixty-five unaffected fetuses (83.33%) and 13 affected fetuses (16.67%) were confirmed in our study. The characteristic metabolites including propionylcarnitine (C3) level, C3/acetylcarnitine (C2) ratio and 2-methylcitric acid (2MCA) level in unaffected and affected groups showed significant differences (P< 0.0001), while the level of 3-hydroxypropionic acid (3HPA) showed no significant difference between the two groups (P> 0.05).Of the 78 pregnancies, 24 fetuses were found to have either one causative pathogenic variant or were without genetic information in the proband. Three of these fetuses had elevated AF levels of C3, C3/C2 ratio, and 2MCA and, thus, were determined to be affected, while the remaining fetuses were determined to be unaffected based on a normal AF metabolite profile. Our genetic and biochemical results were highly consistent with postnatal follow-up results on all unaffected fetuses.ConclusionsWe conclude that a biochemical approach can serve as a fast and convenient prenatal diagnostic method for pregnancies at an increased risk for PA, which could be used in conjunction with genetic testing for precise prenatal diagnosis of this disorder. In our analysis, the characteristic metabolites C3 level, C3/C2 ratio, and 2MCA level in AF supernatant were dependable biochemical markers for diagnosis, of which the C3/C2 ratio appears to be the most reliable biochemical marker for the prenatal diagnosis of PA.
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DOI：
10.3760/cma.j.issn.1003-9406.2015.01.006
发表时间：
2015-02-01
期刊：
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics
影响因子：
--
作者：
Chen, Zhanling;Wen, Pengqiang;Li, Chengrong
通讯作者：
Li, Chengrong
DOI：
10.1016/j.jchromb.2005.04.020
发表时间：
2005-08-25
影响因子：
3
作者：
Hasegawa, Y;Iga, M;Yamaguchi, S
通讯作者：
Yamaguchi, S
丙酸血症的急性治疗。
影响因子：
3.8
作者：
Chapman, Kimberly A.;Gropman, Andrea;MacLeod, Erin;Stagni, Kathy;Summar, Marshall L.;Ueda, Keiko;Mew, Nicholas Ah;Franks, Jill;Island, Eddie;Matern, Dietrich;Pena, Loren;Smith, Brittany;Sutton, V. Reid;Urv, Tiina;Venditti, Charles;Chakrapani, Anupam
通讯作者：
Chakrapani, Anupam
利用遗传和生化方法对羊水甲基丙二酸尿症进行产前诊断
影响因子：
3
作者：
Ji, Xing;Wang, Huanhuan;Han, Lianshu
通讯作者：
Han, Lianshu
影响因子：
3.7
作者：
Chu, Tzu-Hung;Chien, Yin-Hsiu;Niu, Dau-Ming
通讯作者：
Niu, Dau-Ming