运用二代测序技术产前诊断ZMPSTE24基因突变

发布时间：2018-04-21 01:32

本文选题：绒毛膜羊膜分离 + 二代测序技术　；参考：《中山大学学报(医学科学版)》2017年03期

【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.1006GC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.1006GC)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。
[Abstract]:[objective] to investigate the role of second-generation sequencing combined with Sanger sequencing in the detection of pathogenic genes in a pedigree with primary partial chorionic membrane pathological separation. To explore the idea and method of prenatal diagnosis for clinical rare fetal diseases. [methods] two pathogenicity mutations were found in the ZMPSTE24 gene by high throughput sequencing of the whole gene exon. The pathogenicity sites of the proband and their parents were confirmed by Sanger sequencing. After the pathogenicity sites were identified, the third trimester fetuses were diagnosed by villi sampling. [results] it was detected that the proband had frame shift mutation on exon 10 of ZMPSTE24 gene, deletion of AGC1389 to c.1390 (from mother) and missense mutation on exon 8 of ZMPSTE24 gene, c. 1006GC double heterozygosity. From the father. The results of prenatal diagnosis of second pregnancy suggest that the fetus is a carrier of gene mutation c. 1006GC, and the mutation originates from father. [conclusion] two new mutations of ZMPSTE24 gene were successfully isolated by whole exon sequencing in this study. Early chorionic sampling was performed on a pregnant woman with the same primary partial amniotic membrane separation. The ZMPSTE24 gene mutation was associated with mandibuloacral dysplasia with type B. The new mutation may be the etiology of this primary partial amniotic membrane separation. To provide reference methods and ideas for etiology detection and fetal intrauterine diagnosis of rare diseases.
【作者单位】：广东省妇幼保健院医学遗传中心;广东省妇幼保健院超声科;禅城中心医院妇产科;
【基金】：广东省医学科学技术研究基金(20121018440105197311060029)
【分类号】：R440;R714.5

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