Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Eugenic and Perinatal Institute, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Prenat Diagn. 2020 Sep;40(10):1228-1238. doi: 10.1002/pd.5732. Epub 2020 May 28.
To assess the value of chromosome microarray analysis (CMA) and whole exome sequencing (WES) in fetuses with cerebellar vermis defects (CVD).
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).
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.
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.
评估染色体微阵列分析（CMA）和全外显子测序（WES）在小脑蚓部缺陷（CVD）胎儿中的应用价值。
2013 年至 2019 年，我们对 43 例 CVD 胎儿进行了 CMA 分析，根据形态学亚型将其分为小脑蚓部发育不良（CVH）组和 Dandy-Walker 畸形（DWM）组。随后，对 19 例 CMA 结果正常的胎儿进行 WES，以鉴定诊断性遗传变异（DGVs）。
23.3%（10/43）的胎儿中发现了染色体非整倍体和临床意义上的拷贝数变异，多发畸形胎儿的阳性率明显高于单发畸形胎儿（36%比 5.6%，P=0.028）。Xq25 重复综合征相关的 STAG2 基因可能是 CVD 的一个新候选基因。在 19 例检测的胎儿中，WES 在 7 个基因中检测到 8 个 DGVs。常染色体隐性纤毛病（4/8）由 TMEM231、CSPP1 和 CEP290 突变引起，是最常见的单基因疾病，其次是 Opitz GBBB 综合征（2/8）由 MID1 和 SPECC1L 变异引起。
CMA 和 WES 的联合应用有可能为 42%（18/43）的胎儿 CVD 提供遗传诊断。当 CMA 结果正常时，应进行 WES。
