Predictors of whole exome sequencing in dystonic cerebral palsy and cerebral palsy-like disorders.
Predictors of whole exome sequencing in dystonic cerebral palsy and cerebral palsy-like disorders.
复制标题
肌张力障碍性脑瘫和脑瘫样疾病的全外显子组测序的预测因子。
DOI：
10.1016/j.parkreldis.2023.105352
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发表时间：
2023
影响因子：
4.1
通讯作者：
M. Škorvánek
中科院分区：
文献类型：
--
作者：
P. Pavelekova;J. Necpál;R. Jech;P. Havránková;J. Švantnerová;V. Jurková;Z. Gdovinová;A. Lackova;V. Han;J. Winkelmann;M. Zech;M. Škorvánek
脑性瘫痪(CP)是一组因胎儿或婴儿大脑发育中的非进行性障碍而引起的永久性疾病。脑性瘫痪样(CP样)疾病在临床上可能类似于CP，但不符合CP标准，通常具有进行性病程和/或神经发育退化。为了评估哪些肌张力障碍和肌张力障碍样障碍患者应该接受全外显子组测序，我们比较了个体在临床表现、合并症和环境危险因素方面可能的致病变异率。方法根据临床表现和病程将以肌张力障碍为核心特征的早发性神经发育障碍(ND)患者分为CP组和CP样组。结果122例患者分为脑性瘫痪组70例(男性30例，平均年龄18y5m±16y6m，GMFCS评分3.3m±81.4m)，类脑性瘫痪组52例(男性29例，平均年龄17y7m±1y，6m，平均GMFCS评分2，6±1，5)。基于WES的诊断出现在19例(27.1%)CP患者和30例(57.7%)CP样患者(57.7%)，两组遗传条件重叠。我们发现有危险因素的CP患者和无危险因素的CP患者的诊断率有显著差异(13.9%比43.3%)；Fisher‘s精确p=0.0065。而CP样者则无此倾向(45.5%vs58.5%)，Fisher‘s确切P值=0.50。结论WES是诊断肌张力障碍型ND的有效方法，无论其表现为CP或CP样表型。
IntroductionCerebral palsy (CP) is a group of permanent disorders attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. Cerebral palsy-like (CP-like) disorders may clinically resemble CP but do not fulfill CP criteria and have often a progressive course and/or neurodevelopmental regression. To assess which patients with dystonic CP and dystonic CP-like disorder should undergo Whole Exome Sequencing (WES), we compared the rate of likely causative variants in individuals regarding their clinical picture, co-morbidities, and environmental risk factors.MethodIndividuals with early onset neurodevelopmental disorder (ND) manifesting with dystonia as a core feature were divided into CP or CP-like cohorts based on their clinical picture and disease course. Detailed clinical picture, co-morbidities, and environmental risk factors including prematurity, asphyxia, SIRS, IRDS, and cerebral bleeding were evaluated.ResultsA total of 122 patients were included and divided into the CP group with 70 subjects (30 males; mean age 18y5m±16y6m, mean GMFCS score 3.3 ± 1.4), and the CP-like group with 52 subjects (29 males; mean age 17y7m±1y,6 m, mean GMFCS score 2,6 ± 1,5). The WES-based diagnosis was present in 19 (27.1%) CP patients and 30 CP-like patients (57.7%) with genetic conditions overlap in both groups. We found significant differences in diagnostic rate in CP individuals with vs. without risk factors (13.9% vs. 43.3%); Fisher's exact p = 0.0065. We did not observe the same tendency in CP-like (45.5% vs 58.5%); Fisher's exact p = 0.5.ConclusionWES is a useful diagnostic method for patients with dystonic ND, regardless of their presentation as a CP or CP-like phenotype.
影响因子：
120.7
作者：
Moreno-De-Luca, Andres;Millan, Francisca;Martin, Christa L.
通讯作者：
Martin, Christa L.