3例16p11.2微缺失综合征胎儿的产前诊断及其产前超声分析*

目的 分析3例16p11.2微缺失综合征胎儿的临床资料,探讨其产前诊断方法及宫内表型。方法回顾3例产前诊断为16p11.2微缺失（593?kb）胎儿的染色体核型分析、单核苷酸多态性微阵列（SNP微阵列）检测结果,分析这3例胎儿的产前超声特点。结果 病例1和病例2胎儿羊水染色体核型为46,XX,病例3胎儿羊水染色体核型为46,XY。病例1的SNP微阵列结果为arr[hg19]16p11.2（29,428,531～30,350,748）X1,即16p11.2存在922?kb的缺失。病例2的SNP微阵列结果为arr[hg19]16p11.2（29,591,326～30,176,508）X1,即16p11.2存在585?kb的缺失。病例3的SNP微阵列结果为arr[hg19]16p11.2（29,428,531～30,176,508）X1,即16p11.2存在748?kb的缺失。3例均有关键区域缺失,包含PRRT2、KCTD13、TBX6、HIRIP3、SEZ6L2等候选致病基因。病例1、2产前超声均提示胎儿半椎体畸形、脊柱侧弯,病例3产前超声提示胎儿颈部半透明膜增厚。结论 16p11.2微缺失综合征在产前可出现各个系统超声异常,但椎体畸形最为常见。中国汉族人群产前超声中如果出现胎儿半椎体畸形、脊柱侧弯,应考虑16p11.2微缺失综合征的可能。SNP微阵列分析可以有效地诊断16p11.2微缺失综合征,明确其断裂点以及所涉及的基因,有助于分析其基因型与表型的对应关系。

Prenatal diagnosis and prenatal phenotypes of 16p11.2 deletion syndrome*

Objective To analyze 3 cases of 16p11.2 deletion syndrome diagnosed prenatally, and to define the prenatal phenotypes of this syndrome. Methods The results of G-banded karyotyping and single nucleotide polymorphism array (SNP array) of 3 fetuses with 16p11.2 deletion syndrome were reviewed and the prenatal ultrasound of these 3 fetuses were analyzed. Results All amniocenteses revealed normal karyotype. Whereas SNP array detected a 922?kb deletion at 16p11.2 [arr [hg19] 16p11.2 (29, 428, 531-30, 350, 748) X1] in fetus 1, a 585?kb deletion at 16p11.2 [arr [hg19] 16p11.2 (29, 591, 326-30, 176, 508) X1]in fetus 2, and a 748 kb deletion at 16p11.2 [arr [hg19] 16p11.2 (29, 428, 531-30, 176, 508) X1] in fetus 3. All deletions have overlapped with the critical region of chromosome 16p11.2 deletion syndrome and involved candidate genes such as PRRT2, KCTD13, TBX6, HIRIP3 and SEZ6L2. Prenatal ultrasound of fetus 1 and 2 showed hemirertebra and scoliosis, and prenatal ultrasound of fetus 3 showed increased nuchal translucency (NT). Conclusions Chromosome 16p11.2 deletion syndrome could be seen in several types of prenatal ultrasound abnormalities, and vertebral anomalies are the most frequent. If the prenatal ultrasound showed hemirertebra and scoliosis in Chinese Han population, chromosome 16p11.2 deletion syndrome could be put into consideration. SNP array can efficiently detect chromosome 16p11.2 deletion syndrome and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations.