Genetic tests aid in counseling of fetuses with cerebellar vermis defects
Genetic tests aid in counseling of fetuses with cerebellar vermis defects
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基因测试有助于对患有小脑蚓部缺陷的胎儿进行咨询
DOI：
10.1002/pd.5732
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发表时间：
2020-05-28
影响因子：
3
通讯作者：
Liao, Can
中科院分区：
文献类型：
--
作者：
Li, Lushan;Fu, Fang;Liao, Can
目的探讨染色体微阵列分析（CMA）和全外显子组测序（WES）在小脑蚓部缺陷（CVD）胎儿中的应用价值。结果23.3%（10/43）的胎儿存在染色体非整倍体和有临床意义的拷贝数变异，其中多发畸形胎儿的染色体非整倍体和有临床意义的拷贝数变异检出率显著高于单纯畸形胎儿（36%vs5.6%，P = 0.028）。与Xq 25重复综合征相关的STAG 2基因可能是CVD的新候选基因。WES在测试的19个胎儿中检测到7个基因中的8个DGV。TMEM 231、CSPP 1和CEP 290突变引起的常染色体隐性纤毛病（4/8）是最常见的单基因遗传病，其次是MID 1和SPECC 1 L突变引起的Opitz GBBB综合征（2/8）。当CMA结果正常时，应提供WES。
Objective To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD).Methods From 2013 to 2019, we performed CMA on 43 fetuses with CVD, who were divided into cerebellar vermis hypoplasia (CVH) group and Dandy-Walker malformation (DWM) group according to morphological subtypes. Subsequently, WES was performed on 19 fetuses with normal CMA results to identify diagnostic genetic variants (DGVs).Results Chromosome aneuploidies and clinically significant copy number variants were identified in 23.3% (10/43) of fetuses, and a significantly higher positive rate was found in fetuses with multiple compared with isolated malformations (36% vs 5.6%, P = .028). STAG2 genes related to Xq25 duplication syndrome was possibly a novel candidate gene for CVD. WES detected eight DGVs in seven genes among the 19 fetuses tested. Autosomal recessive ciliopathies (4/8) caused by TMEM231, CSPP1, and CEP290 mutations, were the most frequent monogenetic diseases, followed by Opitz GBBB syndrome (2/8) caused by MID1 and SPECC1L variants.Conclusion The combined use of CMA and WES has the potential to provide genetic diagnoses in 42% (18/43) of fetal CVD. WES should be offered when CMA results are normal.