多种遗传学技术联合运用对疑似Meckel综合征家系进行遗传学分析

目的：对1例临床疑似Meckel综合征的引产胎儿组织进行遗传学分析，为该家系的遗传咨询和再生育提供遗传学依据。方法：采用比较基因组杂交芯片和全外显子组测序对引产胎儿组织进行遗传学检测，用Sanger测序验证胎儿父母及姐妹的致病位点。结果：染色体微阵列芯片检查未发现大于100 kb拷贝数变异，排除胎儿因染色体数目及拷贝数变异致病原因；全外显子测序显示胎儿携带CC2D2A基因c.3964C＞T和c.4567T＞C复合杂合变异，Sanger测序确认变异分别来自于父母，其表型正常的姐姐存在c.3964C＞T杂合突变。结论：CC2D2A基因c.3964C＞T和c.4567T＞C复合杂合突变为该家系Meckel综合征的致病原因，多种遗传学技术联合运用对表型相似的疾病进行鉴别诊断，为该家系的遗传咨询和产前诊断或胚胎植入前诊断提供了遗传学依据，对寻找可能的致病基因具有重要意义。

Mutation of a suspected Meckel-Gruber Pedigree: a multiple genetics analysis

Objective: To make a genetic analysis of a case of fetal tissue induced by clinically suspected Meckel syndrome so as to provide the family with genetic counseling and re-fertility suggestions. Methods: The comparative genomic hybridization (CGH) and whole exon sequencing (WES) technology was used for detecting the genetic mutation of the fetal tissues, and Sanger sequencing was used to verify the pathogenic sites of fetal parents and sisters. Results: Chromosomal microarray showed no obvious abnormality. WES showed the fetus carried the CC2D2A gene c.3964C>T and c.4567T>C compound heterozygous variation. Conclusion: CC2D2A gene c.3964C>T and c.4567T>C compound heterozygous mutations are the cause of Meckel syndrome in this family. Combination of different techniques can be applied to find disease-causing gene mutations and give a sufficient evidence for genetic consultation, prenatal diagnosis or pre-implantation genetic diagnosis.