利用纳米孔测序技术准确产前诊断面囊肱肌营养不良症1。

IF 3.5 2区 医学 Q2 GENETICS & HEREDITY Journal of Medical Genetics Pub Date : 2024-10-26 DOI:10.1136/jmg-2023-109832
Yanan Wang, Zhenhua Zhao, Fei Meng, Xiangdong Kong
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引用次数: 0

摘要

背景:面岬肱肌营养不良症 1(FSHD1)是一种常染色体显性遗传的肌肉疾病,主要由染色体 4q35 上的 D4Z4 重复序列收缩和低甲基化引起。由于基因组结构高度重复且较长,FSHD1的产前诊断具有挑战性。在本研究中,一位孕妇通过光学基因组图谱诊断出患有 FSHD1,并希望获得健康的后代:在妊娠第 17 周时,她接受了羊膜穿刺术,并从羊膜细胞中提取了基因组 DNA(gDNA)。利用纳米孔 MinION 平台对 gDNA 进行了全基因组测序:结果:尽管测序深度仅为 7.3 倍,但生物信息学分析表明,胎儿从母亲那里遗传了 4 个 D4Z4 重复单位,其中 4qA 为允许遗传,而从父亲那里遗传了 8 个 D4Z4 重复单位,其中 4qB 为非允许遗传。为了验证这一结果,研究人员对来自疑似胎儿、疑似胎儿父亲和疑似胎儿羊膜细胞的 gDNA 进行了基于 SNP 的关联分析。结果表明,基于 144 个信息 SNP,胎儿遗传了母体的致病单倍型。关联分析与纳米孔测序结果一致:结论:纳米孔测序被证明是在单核苷酸水平上对单基因遗传病进行基因检测的一种准确而直接的方法。这项研究是纳米孔测序技术在 FSHD1 产前诊断中的首次应用,为新发基因突变患者提供了显著优势。
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Accurate prenatal diagnosis of facioscapulohumeral muscular dystrophy 1 using nanopore sequencing.

Background: Facioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant muscular disorder mainly caused by the contraction and hypomethylation of the D4Z4 repeat array in chromosome 4q35. Prenatal diagnosis of FSHD1 is challenging due to the highly repetitive and long genomic structure. In this study, a pregnant woman diagnosed with FSHD1 using optical genome mapping sought assistance for a healthy offspring.

Methods: At the 17th week of gestation, she underwent amniocentesis, and genomic DNA (gDNA) was extracted from amniocytes. Whole-genome sequencing of the gDNA was performed using the nanopore MinION platform.

Results: Despite a sequencing depth of only 7.3×, bioinformatic analyses revealed that the fetus inherited four D4Z4 repeat units with the permissive 4qA from the mother and the eight D4Z4 repeat units with the non-permissive 4qB from the father. To validate the results, SNP-based linkage analyses were conducted with gDNA from the proband, the proband's father and proband's amniocytes. Results indicated that the fetus inherited the maternal pathogenic haplotype based on 144 informative SNPs. Linkage analysis was consistent with the nanopore sequencing.

Conclusion: Nanopore sequencing proves to be an accurate and direct method for genetic testing of monogenic diseases at the single-nucleotide level. This study represents the first application of nanopore sequencing in the prenatal diagnosis of FSHD1, providing a significant advantage for patients with de novo mutations.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
期刊最新文献
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