aCGH应用于产前诊断意外发现DMD基因缺失或重复病例分析

Case analysis of accidental discovery of DMD gene deletion or duplication using aCGH in prenatal diagnosis

摘要

目的 探讨微阵列比较基因组杂交(aCGH)技术应用在产前诊断中发现抗肌萎缩蛋白基因(又称DMD基因)缺失或重复的重要价值。方法 收集2019年9月至2020年7月在西北妇女儿童医院因高危因素(高龄、血清学筛查高风险、无创筛查高风险或超声软指标异常等)选择aCGH技术进行产前诊断的851例孕妇的羊水样本进行检测,并进一步采用多重连接探针扩增(MLPA)方法对DMD基因变异样本进行验证。结果 在851例孕妇的羊水样本中,经aCGH产前诊断时意外发现4例羊水样本存在DMD基因缺失或重复,同时MLPA检测验证了上述变异.胎儿1:男胎,arr[GRCh37]Xp21.1(31691172-31766673)×0,DMD基因E52-53缺失;胎儿2:男胎,arr[GRCh37]Xp21.2(31016983-31351900)×2,DMD基因E61-79重复;胎儿3:女胎,arr[GRCh37]Xp21.2(31182699-31474949)×3,DMD基因E58-74重复;胎儿4:男胎,arr[GRCh37]Xp21.1(31777925-32152126)×2,DMD基因E45-51重复.4例变异均遗传自母亲。结论 产前诊断是防止DMD患者出生的重要手段,aCGH技术用于产前诊断不仅可以检测染色体微缺失和微重复综合征,还有助于检测由基因缺失或重复引起的单基因疾病,从而为临床诊断及遗传咨询提供了理论依据.

Abstract

Objective To explore the important value of array comparative genomic hybridization (aCGH) technology in prenatal diagnosis for the detection of deletions or duplications in the dystrophin gene (also known as the DMD gene). Methods Amniotic fluid samples from 851 pregnant women who underwent prenatal diagnosis using aCGH technology due to high-risk factors (such as advanced maternal age, high-risk serum screening, high-risk non-invasive screening, or abnormal ultrasound soft markers) at Northwest Women's and Children's Hospital from September 2019 to July 2020 were collected for testing. Furthermore, the multiplex ligation-dependent probe amplification (MLPA) method was used to validate DMD gene variations. Results Among the 851 amniotic fluid samples from pregnant women, aCGH prenatal diagnosis unexpectedly revealed 4 cases of DMD gene deletions or duplications. Subsequent MLPA testing confirmed the above variations. Fetus 1: male, arr[GRCh37]Xp21.1(31691172-31766673)×0, DMD gene E52-53 deletion; Fetus 2: male, arr[GRCh37]Xp21.2(31016983-31351900)×2, DMD gene E61-79 duplication; Fetus 3: female, arr[GRCh37]Xp21.2(31182699-31474949)×3, DMD gene E58-74 duplication; Fetus 4: male, arr[GRCh37]Xp21.1(31777925-32152126)×2, DMD gene E45-51 duplication. All 4 variations were inherited from the mothers. Conclusion Prenatal diagnosis is an important means to prevent the birth of DMD patients. The application of aCGH technology in prenatal diagnosis not only detects chromosomal microdeletions and microduplications syndromes but also helps to detect single-gene diseases caused by gene deletions or duplications, providing a theoretical basis for clinical diagnosis and genetic counseling.

关键词

微阵列比较基因组杂交 / 抗肌萎缩蛋白基因 / 产前诊断 / 多重连接探针扩增

Key words

array comparative genomic hybridization / dystrophin gene / prenatal diagnosis / multiplex ligation-dependent probe amplification

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基金资助

国家自然科学基金项目(82201865)

陕西省重点研发计划项目(2023GYBSFG305)