国际生殖健康/计划生育杂志

国际生殖健康/计划生育 ›› 2022, Vol. 41 ›› Issue (1): 12-17.doi: 10.12280/gjszjk.20210326

• 论著 • 上一篇    下一篇

帕金森病15型基因突变携带者行胚胎植入前单基因遗传学检测助孕成功一例

王志强, 倪亚莉(), 安锦霞, 王同光, 张风霞   

  1. 730050 兰州,甘肃省妇幼保健院生殖医学中心
  • 收稿日期:2021-07-21 出版日期:2022-01-15 发布日期:2022-02-17
  • 通讯作者: 倪亚莉 E-mail:niyali@126.com
  • 基金资助:
    甘肃省自然科学基金(20JR5RA138)

A Case of Preimplantation Genetic Testing for Monogenic Parkinson′s Disease Type 15 Caused by Mutation of FBXO7

WANG Zhi-qiang, NI Ya-li(), AN Jin-xia, WANG Tong-guang, ZHANG Feng-xia   

  1. Reproductive Medical Center, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, China
  • Received:2021-07-21 Published:2022-01-15 Online:2022-02-17
  • Contact: NI Ya-li E-mail:niyali@126.com

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摘要：

目的： 对携带FBXO7（F-box only protein 7）基因突变的夫妇行胚胎植入前单基因遗传学检测（Preimplantation Genetic Testing for Monogenic Disorders,PGT-M）,以阻断帕金森病15型致病基因向子代传递。方法： 在1个携带FBXO7基因突变的家系中,对先证者FBXO7基因的突变位点c.402G>A和c.872-1G>A进行Sanger测序验证,并且在该家系的基因组DNA（genomic DNA,gDNA）样本中进行FBXO7基因上下游2 Mb范围内单核苷酸多态性（single nucleotide polymorphism,SNP）多重扩增,以构建家系SNP单体型,从而区分携带致病突变的单体型。通过控制性卵巢刺激获取卵母细胞,行卵细胞质内单精子注射（intracytoplasmic sperm injection,ICSI）及胚胎培养,至第5~6天行囊胚滋养层细胞活检。经PGT-M技术后,选择不致病胚胎移植。结果： 本周期共获卵15枚,ICSI后正常受精9枚,通过囊胚培养形成5枚可活检囊胚。活检示5枚囊胚均成功扩增,胚胎非整倍性检测显示其中2枚胚胎染色体为非整倍体,剩余3枚胚胎为二倍体。但其中2枚携带父源突变,1枚为同时携带父源和母源复合杂合突变的胚胎。母亲在冻融胚胎移植周期移植1枚携带父源突变的胚胎（形态学评分为5BB）并成功妊娠。妊娠期经过胎儿颈项透明层厚度（nuchal translucency,NT）、系统B超和羊水穿刺三联筛查证实与前期PGT-M胚胎检测结果一致。于2020年4月3日产下一携带父源突变但不致病的男婴。结论： PGT-M技术可帮助FBXO7基因突变导致的常染色体隐性遗传性帕金森病家庭获得健康子代,阻断该基因突变向子代垂直传递。

关键词: 帕金森病, 基因, 突变, 植入前诊断, 精子注射,细胞质内

Abstract:

Objective: The preimplantation genetic testing for monogenic disorders (PGT-M) was performed on couples carrying FBXO7 (F-box only protein 7) gene mutation to block the transmission of Parkinson′s disease type 15 gene mutation to their offspring. Methods: For a case with FBXO7 gene mutation, Sanger sequencing was performed to verify the mutation sites c.402G>A and c.872-1G>A of FBXO7 gene in the proband. In addition, multiple SNP amplification was carried out in the range of 2 Mb upstream and downstream of FBXO7 gene in this family. And the SNP haplotype analysis was carried out to distinguish the haplotype carried by the proband. After controlled ovulation induction, intracytoplasmic sperm injection (ICSI) and embryo culture were performed. Blastocysts were formed from Day5 to Day6, and blast trophoblast cell biopsy was performed. After PGT-M technology and related gene analysis, embryo transfer was selected to block the transmission of PD type 15 mutant gene to offspring. Results: A total of 15 oocytes were obtained in this period, and 9 oocytes were fertilized normally after ICSI fertilization, and 5 biopsy blastocysts were formed after blastocyst culture, and 5 blastocysts were successfully expanded after biopsy. The results showed that 2 embryo chromosomes were aneuploidy, 2 of the 3 blastocysts had paternal mutation, and 1 embryo was sick. One carrier embryo which was evaluated as 5BB by morphology was transferred during the frozen-thawed embryo transfer cycle and pregnancy was successful. The results of NT, B-ultrasound and amniocentesis were consistent with the results of PGT-M embryo test. The male healthy baby was born on April 3, 2020. Conclusions: For autosomal recessive Parkinson′s syndrome caused by FBXO7 gene mutation, PGT-M assisted reproductive technology can successfully block the vertical transmission of the gene mutation to the offspring, and help families with FBXO7 type Parkinson′s syndrome to obtain healthy offspring.

Key words: Parkinson disease, Genes, Mutation, Preimplantation diagnosis, Sperm injections,intracytoplasmic