68例小头畸形胎儿的超声特点及遗传学分析

Prenatal ultrasound features and genetic analysis of 68 fetuses with microcephaly

目的:探讨遗传学检测技术在不同超声表征小头畸形胎儿中的应用价值。方法:收集2018年1月至2022年4月在深圳市妇幼保健院产前诊断中心就诊68例小头畸形胎儿的超声资料与遗传学检测结果。68例胎儿均行染色体微阵列分析(CMA),16例胎儿行全基因外显子组测序(WES)。根据胎儿超声异常特点,将其分为孤立型小头畸形和非孤立性型小头畸形(包括颅脑结构异常型、颅外结构异常型和其他超声异常型小头畸形),并对各组超声异常胎儿的遗传学检测结果进行比较。结果:小头畸形胎儿的遗传学异常检出率为25.00%(17/68),CMA在小头畸形胎儿中的遗传学异常检出率为14.71%(10/68),WES在CMA正常小头畸形胎儿中的异常检出率为46.67%(7/15)。非孤立型小头畸形胎儿的遗传学异常检出率显著高于孤立型小头畸形胎儿(36.36%vs 14.29%,P=0.036),非孤立型小头畸形各组间总体异常检出率差异无统计学意义(χ^(2)=5.142,P=0.102)。结论:非孤立型小头畸形胎儿的染色体异常检出率显著高于孤立型小头畸形。对于CMA正常的小头畸形胎儿,可通过WES检测来提高其遗传学异常检出率。

Objective:To investigate the value of the genetic diagnosis in microcephaly-fetuses with different ultrasound abnormalities.Methods:From January 2018 to April 2022,a total of sixty-eight fetuses with microcephaly from Shenzhen Maternity and Child Healthcare Hospital were collected and their ultrsound and genetic findings were studied.Chromosomal microarray analysis(CMA)had been performed for all of six-eight cases,and whole exome sequencing(WES)had been performed for the other sixteen cases.According to the characteristics of fetal ultrasound abnormalities,the sixty-eight cases were divided into groups of isolated microcephaly and non-isolated microcephaly(including craniocerebral structural abnormalities,extracranial structural abnormalities and other ultrasonic abnormalities).The genetic results were compared between the two groups.Results:The rate of genetical abnormalities was 25.00%(17/68),in which the copy number variants were 10 cases detected by CMA and monogenic variants were 7 cases detected by WES.The rate of genetic abnormalities in the group of fetuses with isolated microcephaly was significantly higher than that group of the fetuses with non-isolated microcephaly(36.36%vs 14.29%,P=0.036).There was no significant differences within the subgroups of fetuses with non-isolated microcephaly(χ^(2)=5.142,P=0.102).Conclusion:The rate of genetical abnormalities in isolated microcephaly was significantly higher than that in non-isolated microcephaly.WES can increase the positive detection rate for the microcephaly-fetuses with negative CMA results.