Department of Laboratory Diagnostcs, Children's Hospital Zagreb, Zagreb, Croatia; Universitas Studiorum Catholica Croatica, Zagreb, Croatia; University of Applied Health Sciences Zagreb, Zagreb, Croatia.
University of Applied Health Sciences Zagreb, Zagreb, Croatia; Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Pediatr Neurol. 2023 Sep;146:119-128. doi: 10.1016/j.pediatrneurol.2023.06.017. Epub 2023 Jun 28.
We aimed to examine inherited thrombophilia frequencies by extending genetic profile to previously rarely or not investigated polymorphisms in children with ischemic pediatric stroke (IPS) and their parents.
The study included 33 children: 23 with perinatal arterial ischemic stroke (PAIS), eight with childhood arterial ischemic stroke (CAIS), and two with sinovenous thrombosis and their parents (33 mother-child, 12 father-child, and 12 mother-father-child pairs). Genotyping of FV-Leiden, FV-H1299R, FII-G20210A, β-fibrinogen-455G>A, FXIII-A-Val34Leu, PAI-1(4G/5G), HPA-1, MTHFR-C677T, MTHFR-A1298C, ACE(I/D), and APOE(ε2-4) was performed using CVD Strip assay (ViennaLab, Austria).
At least one and up to seven simultaneously present polymorphisms were observed in all children with IPS, mothers, and fathers. More than five simultaneously present polymorphisms were identified threefold more frequently in children with IPS (10 of 33; 30%) compared with the child control group (17 of 150; 11%), yielding a statistically significant difference between the two groups (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.39 to 8.35; P = 0.012). Stronger association was revealed for PAIS (OR = 4.17; 95% CI = 1.55 to 11.29; P = 0.008) and CAIS subgroups (OR = 7.82; 95% CI = 1.79 to 34.20; P = 0.012). Complete match of polymorphisms was not identified in any parent-child pair. A partial match (one to four mutual polymorphisms) was found in 11 of 12 parent-child pairs where until three mutual polymorphisms was present in 11 of 12 (91.7%) father-child compared with 21 of 33 (63.6%) mother-child pairs.
According to obtained results the simultaneous presence of more than five polymorphisms is associated with a higher risk for IPS occurrence, suggesting the risk enhancement for PAIS in the presence of pregnancy complications or for CAIS in conjunction with maternal comorbidity and positive family history. The presence of up to three mutual polymorphisms more frequently in father-child than mother-child pairs suggests significant paternal contribution of inherited thrombophilia to increased risk of IPS.
我们旨在通过扩展遗传谱，研究缺血性儿科脑卒中（IPS）患儿及其父母中以前很少或未研究过的遗传性血栓形成倾向的频率。
该研究纳入了 33 名儿童：23 名围产期动脉缺血性脑卒中（PAIS）患儿、8 名儿童期动脉缺血性脑卒中（CAIS）患儿、2 名静脉窦血栓形成患儿及其父母（33 对母子、12 对父子、12 对父母-子女）。使用 CVD Strip 检测试剂盒（奥地利 ViennaLab）对 FV-Leiden、FV-H1299R、FII-G20210A、β-纤维蛋白原-455G>A、FXIII-A-Val34Leu、PAI-1(4G/5G)、HPA-1、MTHFR-C677T、MTHFR-A1298C、ACE(I/D)和 APOE(ε2-4)进行基因分型。
所有 IPS 患儿、母亲和父亲均存在至少一种且多达七种同时存在的突变。与儿童对照组（17/150；11%）相比，IPS 患儿（10/33；30%）更常同时存在超过五种突变，两组间存在统计学显著差异（比值比[OR] = 3.40；95%置信区间[CI] = 1.39 至 8.35；P = 0.012）。PAIS（OR = 4.17；95% CI = 1.55 至 11.29；P = 0.008）和 CAIS 亚组（OR = 7.82；95% CI = 1.79 至 34.20；P = 0.012）的关联更强。在任何一对父母-子女中均未发现突变完全匹配。在 12 对父母-子女中发现了 11 对存在部分匹配（一种至四种共同突变），其中 11 对父母-子女中存在三种共同突变（11/12；91.7%），而 33 对母亲-子女中仅 21 对存在三种共同突变（21/33；63.6%）。
根据所得结果，超过五种突变的同时存在与 IPS 发生的风险增加相关，提示存在妊娠并发症时 PAIS 风险增加，存在母体合并症和阳性家族史时 CAIS 风险增加。在父亲-子女中，突变更常存在三种以上（而非母亲-子女），这提示遗传性血栓形成倾向导致 IPS 风险增加，与父亲的作用显著相关。
