Molecular genetic study of triploidy and the hydatidiform mole in pregnancy loss: analysis of 10,000 consecutive cases.

IF 1 Q3 AGRICULTURE, MULTIDISCIPLINARY
V P Pushkarev, A S Masycheva, E A Glazyrina, T E Serebrenikova, V B Chernykh
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引用次数: 0

Abstract

Approximately 10-15 % of clinically recognized pregnancies result in miscarriage, with chromosomal abnormalities identified in about 50 % of early pregnancy losses (PL). Triploidy accounts for approximately 12 % of all chromosomal abnormalities in miscarriages. The additional haploid set of chromosomes in triploidy may be of paternal (diandric triploidy) or maternal (digynic triploidy) origin. Diandric triploidy is associated with a partial hydatidiform mole (PHM), while pregnancies involving diploid embryos with two paternal genomes (and loss of the maternal nuclear genome) are the most common cause of a complete hydatidiform mole (CHM). The hydatidiform mole (HM) is the most prevalent form of gestational trophoblastic disease. Genotyping of products of conception (POC) is currently considered a reliable method for confirming HM and distinguishing its subtypes. The aim of this study was to use DNA genotyping of POCs to detect cases of triploidy, estimate the frequency of HM and its subtypes, and analyze the molecular and clinical characteristics of triploid pregnancies, CHM, and PHM in a Russian population. Between 2018 and 2024, a total of 10,000 consecutive PL cases were analyzed at the Medical Genetic Center Progen (Moscow). The main clinical indications included spontaneous miscarriage, missed miscarriage, and anembryonic pregnancy. DNA genotyping was performed using a five-color multiplex QF-PCR method, which included profiling of 26 autosomal STR markers, as well as DYS437, DXS6809, the SRY gene, and 30 markers from homologous regions located on different chromosomes. CHM was diagnosed based on the homozygosity of all STR markers. Triploidy was identified by analyzing peak area ratios of non-homozygous STR markers, which exhibited characteristic patterns of approximately 2:1 or 1:1:1. In our cohort, chromosomal abnormalities were identified in 58.8 % of all PL cases. Triploidy was detected in 8.3 % of the total sample, representing 14.3 % of all chromosomally abnormal POCs. Diandric triploidy accounted for 43 % of triploid cases. The prevalence of CHM was 0.11 %. The median age of women with triploidy was 32.1 years, and 27.9 years for those with CHM. Given the observed frequencies of PHM and CHM in our cohort, along with the relatively young maternal age associated with these conditions, enhancing current diagnostic protocols for HM - particularly through the incorporation of DNA genotyping of POCs - is essential for the effective prevention and timely diagnosis of post-molar malignant neoplasms in this population.

妊娠丢失三倍体和葡萄胎的分子遗传学研究:1万例连续病例分析。
大约10- 15%的临床确认妊娠导致流产,染色体异常在约50%的早期妊娠丢失(PL)中被发现。三倍体约占流产中所有染色体异常的12%。三倍体中额外的单倍体染色体可能来自父系(双染色体三倍体)或母系(双染色体三倍体)。双三倍体与部分葡萄胎(PHM)有关,而具有两个父亲基因组的二倍体胚胎(以及母亲核基因组的丢失)的妊娠是完全葡萄胎(CHM)的最常见原因。葡萄胎(HM)是最常见的妊娠滋养细胞疾病。受孕产物基因分型(POC)目前被认为是确认HM和区分其亚型的可靠方法。本研究的目的是利用POCs的DNA基因分型检测三倍体病例,估计HM及其亚型的频率,并分析俄罗斯人群三倍体妊娠、CHM和PHM的分子和临床特征。在2018年至2024年期间,在医学遗传中心Progen(莫斯科)连续分析了10,000例PL病例。主要临床指征包括自然流产、漏产、无胎妊娠。采用五色多重QF-PCR方法进行DNA基因分型,包括分析26个常染色体STR标记,以及DYS437、DXS6809、SRY基因和30个来自不同染色体同源区域的标记。根据所有STR标记的纯合性诊断CHM。通过分析非纯合STR标记的峰面积比,鉴定出三倍体,其特征模式约为2:1或1:1:1。在我们的队列中,58.8%的PL病例中发现了染色体异常。在8.3%的总样本中检测到三倍体,占所有染色体异常POCs的14.3%。双染色体三倍体占三倍体病例的43%。CHM的患病率为0.11%。三倍体女性的中位年龄为32.1岁,CHM女性的中位年龄为27.9岁。考虑到在我们的队列中观察到的PHM和CHM的频率,以及与这些疾病相关的相对年轻的母亲年龄,加强目前HM的诊断方案-特别是通过结合POCs的DNA基因分型-对于有效预防和及时诊断该人群的磨牙后恶性肿瘤至关重要。
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来源期刊
Vavilovskii Zhurnal Genetiki i Selektsii
Vavilovskii Zhurnal Genetiki i Selektsii AGRICULTURE, MULTIDISCIPLINARY-
CiteScore
1.90
自引率
0.00%
发文量
119
审稿时长
8 weeks
期刊介绍: The "Vavilov Journal of genetics and breeding" publishes original research and review articles in all key areas of modern plant, animal and human genetics, genomics, bioinformatics and biotechnology. One of the main objectives of the journal is integration of theoretical and applied research in the field of genetics. Special attention is paid to the most topical areas in modern genetics dealing with global concerns such as food security and human health.
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