未经证实:脑瘫(CP)有许多已知的获得性危险因素,但在某些情况下,CP是明显的,没有危险因素(隐源性CP)。早期CP队列研究报告了通过外显子组测序(ES)评估的序列变体和通过染色体微阵列(CMA)评估的拷贝数变体(CNV)的广泛诊断产量。
未经证实:综合新兴的CP遗传学文献,并解决多少比例的CP个体通过ES和CMA患有遗传性疾病的问题。
UNASSIGNED:PubMed对搜索的文章进行了索引,其中包含与CP和ES/CMA有关的相关查询(查询日期,2022年3月15日)。
UNASSIGNED:纳入标准如下:主要研究,有10个或更多不相关个人的案例系列,CP诊断,和用于遗传评估的ES和/或CMA数据。进行非盲法审查。
UNASSIGNED:系统评价和Meta分析指南的首选报告项目用于评估数据质量和有效性。数据由单个观察者提取。
未经评估:对每种模式进行了单独的荟萃分析(ES,CMA)。主要结果是比例/分子诊断产量(发现遗传性疾病的患者人数除以队列中的患者总数)。通过使用随机效应逻辑回归的单比例荟萃分析进行评估。进行了亚组荟萃分析,使用危险因素分类作为亚组。森林地块用于显示个别研究的诊断产量。
未经证实:在CP中ES产量的荟萃分析中,队列(15个研究队列,包括11篇文献中的2,419例个体)中ES的总诊断率为23%(95%CI,15%-34%).隐源性CP队列的诊断率为35%(95%CI,27%-45%),在已知危险因素(非隐源性CP)的队列中,这一比例为7%(95%CI,4%-12%).在CP中CMA产量的荟萃分析中,队列(5个研究队列,包含5篇文献中的294例个体)中CMA的诊断阳性率为5%(95%CI,2%-12%).
UNASSIGNED:本系统评价和荟萃分析的结果表明,对于患有隐源性CP的个体,ES后再进行CMA以鉴定分子障碍可能是必要的。
There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies report a wide range of diagnostic yields for sequence variants assessed by exome sequencing (ES) and copy number variants (CNVs) assessed by chromosomal microarray (CMA).
To synthesize the emerging CP genetics literature and address the question of what percentage of individuals with CP have a genetic disorder via ES and CMA.
Searched articles were indexed by PubMed with relevant queries pertaining to CP and ES/CMA (query date, March 15, 2022).
Inclusion criteria were as follows: primary research study, case series with 10 or more nonrelated individuals, CP diagnosis, and ES and/or CMA data used for genetic evaluation. Nonblinded
review was performed.
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for assessing data quality and validity. Data were extracted by a single observer.
A separate meta-analysis was performed for each modality (ES, CMA). The primary outcome was proportion/molecular diagnostic yield (number of patients with a discovered genetic disorder divided by the total number of patients in the cohort), evaluated via meta-analysis of single proportions using random-effects logistic regression. A subgroup meta-analysis was conducted, using risk factor classification as a subgroup. A forest plot was used to display diagnostic yields of individual studies.
In the meta-analysis of ES yield in CP, the overall diagnostic yield of ES among the cohorts (15 study cohorts comprising 2419 individuals from 11 articles) was 23% (95% CI, 15%-34%). The diagnostic yield across cryptogenic CP cohorts was 35% (95% CI, 27%-45%), compared with 7% (95% CI, 4%-12%) across cohorts with known risk factors (noncryptogenic CP). In the meta-analysis of CMA yield in CP, the diagnostic yield of CMA among the cohorts (5 study cohorts comprising 294 individuals from 5 articles) was 5% (95% CI, 2%-12%).
Results of this systematic
review and meta-analysis suggest that for individuals with cryptogenic CP, ES followed by CMA to identify molecular disorders may be warranted.