【摘要】 【目的】探讨二代测序技术结合Sanger测序验证法在一原发性部分性绒毛膜羊膜病理性分离家系致病基因检测的作用,探索临床罕见胎儿疾病的产前诊断思路与方法。【方法】采用全基因外显子高通量测序方法,在ZMPSTE24基因中发现两个致病突变,随后对先证者及其父母的致病位点进行Sanger测序验证,明确致病位点后,对第3次妊娠胎儿行绒毛取样术实施产前诊断,分析致病位点。【结果】检测到先证者在ZMPSTE24基因第10个外显子上发生了框移突变(c.1389至c.1390缺失AG,来源于母亲)以及在ZMPSTE24基因第8个外显子上发生了错义突变(c.1006G>C双重杂合改变,来源于父亲)。再次妊娠产前诊断结果提示胎儿为基因突变(c.1006G>C)携带者,突变来源于父亲。【结论】本研究运用全外显子测序技术成功分离出ZMPSTE24基因的两个新突变,对一曾出现相同两次原发性部分性绒毛膜羊膜病理性分离的孕妇再次妊娠行早期绒毛取样术产前诊断。该ZMPSTE24基因突变与mandibuloacral dysplasia with type B相关。新突变可能是该原发性部分性绒毛膜羊膜病理性分离病例的病因。为临床上罕见疾病的病因检测及胎儿宫内诊断提供参考方法与思路。更多还原

【Abstract】 【Objective】To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing（NGS）and Sanger sequencing.【Methods】For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing（NGS）and Sanger sequencing. And the prenatal diagnosis were identified by Sanger sequencing.【Results】A frameshifting mutation c.1389₁390del AG（inherited from mother）,and a missense mutationc. 1006 G > C（inherited from mother）have been identified in the affected fetus（the second pregnancy）. The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.【Conclusions】We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation. This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation. And the conbinedcombined next-generation sequencing（NGS）and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.更多还原