胎儿中枢神经系统异常的全外显子组测序。
Whole-exome sequencing in fetuses with central nervous system abnormalities.
机构信息
Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.
Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.
出版信息
J Perinatol. 2018 Oct;38(10):1301-1308. doi: 10.1038/s41372-018-0199-3. Epub 2018 Aug 14.
OBJECTIVE
We describe our experience with whole-exome sequencing (WES) in fetuses with central nervous system (CNS) abnormalities following a normal chromosomal microarray result.
METHODS
During the study period (2014-2017) 7 cases (9 fetuses) with prenatally diagnosed CNS abnormality, whose chromosomal microarray analysis was negative, were offered whole-exome sequencing analysis.
RESULTS
A pathogenic or a likely pathogenic variant was found in 5 cases including a previously described, likely pathogenic de novo TUBA1A variant (Case #1); a previously described homozygous VRK1 variant (Case #2); an X-linked ARX variant (Case #3); a likely pathogenic heterozygous variant in the TUBB3 gene (Case #5). Finally, in two fetuses of the same couple (Case #6), a compound heterozygous state was detected, consisting of the NPHP1 gene deletion and a sequence variant of uncertain significance. Two additional cases had normal WES results.
CONCLUSION
Whole-exome sequencing may improve prenatal diagnosis in fetuses with CNS abnormalities.
目的
我们描述了在染色体微阵列结果正常的情况下，对中枢神经系统（CNS）异常胎儿进行全外显子组测序（WES）的经验。
方法
在研究期间（2014-2017 年），对 7 例（9 例胎儿）经产前诊断为 CNS 异常且染色体微阵列分析结果为阴性的胎儿进行了全外显子组测序分析。
结果
在 5 例中发现了致病性或可能致病性的变异，包括先前描述的、可能致病性的新发 TUBA1A 变异（病例#1）；先前描述的纯合 VRK1 变异（病例#2）；X 连锁 ARX 变异（病例#3）；TUBB3 基因的可能致病性杂合变异（病例#5）。最后，在一对夫妇的两名胎儿中（病例#6），检测到复合杂合状态，包括 NPHP1 基因缺失和意义未明的序列变异。另外两例 WES 结果正常。
结论
全外显子组测序可提高中枢神经系统异常胎儿的产前诊断水平。
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