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早期妊娠丢失中部分染色体异常的描绘

Delineation of Partial Chromosomal Abnormalities in Early Pregnancy Losses.

作者信息

Bozhinovski Gj, Terzikj M, Kubelka-Sabit K, Plaseska-Karanfilska D

机构信息

Research Center for Genetic Engineering and Biotechnology "Georgi D. Efremov", Macedonian Academy of Sciences and Arts, Skopje, North Macedonia, Skopje, North Macedonia.

Clinical Hospital "Acibadem Sistina", Skopje, North Macedonia.

出版信息

Balkan J Med Genet. 2025 Mar 6;27(2):23-32. doi: 10.2478/bjmg-2024-0014. eCollection 2024 Dec.

Abstract

Pregnancy loss (PL), particularly early pregnancy loss (EPL), is a prevalent reproductive complication, with approximately 15% of confirmed pregnancies affected. Chromosomal abnormalities are implicated in more than half of EPLs, with trisomies being the most prevalent. Partial abnormalities, including segmental deletions, duplications, and unbalanced translocations, are detected in up to 10% of EPL cases. This study focuses on the precise characterization of partial chromosomal abnormalities, previously identified by Quantitative fluorescent polymerase chain reaction (QF-PCR) and multiplex ligation probe amplification (MLPA) analyses. By employing an array comparative genomic hybridization (aCGH), we analyzed 20 EPL samples, identifying 32 partial chromosomal abnormalities, including 18 deletions and 14 duplications, with an average size of 33.2 Mb. Notably, two abnormalities previously undetected by QF-PCR and MLPA were revealed (deletions in 7q36, and 1p36.32p36.31regions), emphasizing the necessity of high-resolution genomic tools. Chromosomes 1, 18, and 13 emerged as frequently involved, aligning with previous associations with recurrent pregnancy loss. Recurrent abnormalities were identified in six chromosomal regions, with chromosome 1p36.33-p36.32 exhibiting the highest frequency. Gene Ontology (GO) enrichment analysis of recurrent regions highlighted disruptions in critical biological processes, including molecular binding, enzymatic activity, and cellular development. Many genes in these regions are linked to multisystem syndromes, suggesting their involvement in early embryonic development and pregnancy viability. Our findings underscore the complexity of EPL's genetic landscape, demonstrating that large CNVs, may disrupt multiple genes critical for development. Although, subtelo-meric MLPA reliably detects telomeric partial chromosomal abnormalities in EPLs, aCGH is essential for detection and precise characterization of all CNVs, thus enhancing diagnostic and counseling strategies in affected couples.

摘要

妊娠丢失(PL),尤其是早期妊娠丢失(EPL),是一种常见的生殖并发症,约15%的确诊妊娠会受到影响。超过一半的EPL与染色体异常有关,其中三体最为常见。在高达10%的EPL病例中可检测到部分异常,包括片段缺失、重复和不平衡易位。本研究聚焦于先前通过定量荧光聚合酶链反应(QF-PCR)和多重连接探针扩增(MLPA)分析鉴定出的部分染色体异常的精确特征。通过使用阵列比较基因组杂交(aCGH),我们分析了20个EPL样本,鉴定出32个部分染色体异常,包括18个缺失和14个重复,平均大小为33.2 Mb。值得注意的是,发现了两个先前QF-PCR和MLPA未检测到的异常(7q36以及1p36.32 - p36.31区域的缺失),强调了高分辨率基因组工具的必要性。1号、18号和13号染色体是频繁受累的染色体,这与先前复发性妊娠丢失的关联一致。在六个染色体区域发现了复发性异常,其中1p36.33 - p36.32染色体区域的频率最高。对复发性区域的基因本体(GO)富集分析突出了关键生物学过程的破坏,包括分子结合、酶活性和细胞发育。这些区域的许多基因与多系统综合征相关,表明它们参与早期胚胎发育和妊娠存活。我们的研究结果强调了EPL遗传格局的复杂性,表明大片段拷贝数变异(CNV)可能破坏多个对发育至关重要的基因。虽然亚端粒MLPA能可靠地检测EPL中的端粒部分染色体异常,但aCGH对于检测所有CNV并精确表征其特征至关重要,从而增强对受影响夫妇的诊断和咨询策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e5b/11892934/601b523afdb6/j_bjmg-2024-0014_fig_001.jpg

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