Division of Maternal Fetal Medicine, University of California, San Francisco, CA, USA.
Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
BJOG. 2021 Jan;128(2):431-438. doi: 10.1111/1471-0528.16427. Epub 2020 Aug 18.
To categorise the variants of uncertain significance found with prenatal chromosomal microarray and determine the proportion of such variants that are associated with a well-known phenotype in order to establish how often they remain truly of uncertain significance.
Retrospective cohort study.
The University of California, San Francisco.
All patients with a variant of uncertain significance on prenatal microarray between 2014 and 2018.
Each variant was classified as a copy number variant that (a) contains Online Mendelian Inheritance in Man (OMIM)-annotated disease-causing genes ('OMIM morbid genes'); (b) confers autosomal recessive carrier status; (c) is associated with incomplete penetrance; (d) is >1 Mb in size without OMIM morbid genes; (e) demonstrates mosaicism; or (f) contains significant regions of homozygosity. For each variant of uncertain significance, we examined the existing literature to determine whether the predicted phenotype(s) was known.
Prevalence and classification of variants and how much information is available regarding the likelihood of an affected phenotype.
Of 970 prenatal microarrays, 55 (5.8%) had at least one variant of uncertain significance. The most common were copy number variants containing OMIM morbid genes (36.8%). In all, 48 (84.2%) were associated with a known phenotype; 55 (96.5%) had data available regarding the likelihood of an affected phenotype.
The prevalence of variants of uncertain significance with prenatal microarray was 5.8%. In the large majority of cases, data were available regarding the predicted phenotype.
Variants of uncertain significance occur in 5.8% of prenatal microarrays. In the overwhelming majority of cases, outcome information is available.
对产前染色体微阵列检测发现的意义不明的变异进行分类，并确定与已知表型相关的此类变异的比例，以确定它们在多大程度上仍然存在真正的意义不明。
回顾性队列研究。
加利福尼亚大学旧金山分校。
2014 年至 2018 年间产前微阵列检查中发现意义不明变异的所有患者。
将每个变异分为以下几类：（a）包含在线孟德尔遗传数据库（OMIM）中注释的致病基因的拷贝数变异（“OMIM 病态基因”）；（b）赋予常染色体隐性携带者状态；（c）具有不完全外显率；（d）大小大于 1Mb 但无 OMIM 病态基因；（e）表现为嵌合体；或（f）含有显著的纯合区域。对于每个意义不明的变异，我们查阅了现有文献，以确定预测的表型是否已知。
变异的流行率和分类，以及有关表型出现可能性的信息。
在 970 例产前微阵列中，有 55 例（5.8%）至少有一种意义不明的变异。最常见的是包含 OMIM 病态基因的拷贝数变异（36.8%）。在所有情况下，48 种（84.2%）与已知表型相关；55 种（96.5%）有关于表型出现可能性的数据。
产前微阵列检测发现意义不明的变异的流行率为 5.8%。在绝大多数情况下，都有关于预测表型的信息。
产前微阵列检测发现意义不明的变异发生率为 5.8%。在绝大多数情况下，都有关于表型的结果信息。
