自然流产中通过测序检测到的拷贝数变异分析。

Analysis of copy number variants detected by sequencing in spontaneous abortion.

作者信息

Liu Anhui, Zhou Liyuan, Huang Yazhou, Peng Dan

机构信息

Hengyang Medical School, University of South China, Hengyang, 421000, China.

Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410000, China.

出版信息

Mol Cytogenet. 2024 May 20;17(1):13. doi: 10.1186/s13039-024-00683-3.

DOI:10.1186/s13039-024-00683-3

PMID:38764094

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11103966/

Abstract

BACKGROUND

The incidence of spontaneous abortion (SA), which affects approximately 15-20% of pregnancies, is the most common complication of early pregnancy. Pathogenic copy number variations (CNVs) are recognized as potential genetic causes of SA. However, CNVs of variants of uncertain significance (VOUS) have been identified in products of conceptions (POCs), and their correlation with SA remains uncertain.

RESULTS

Of 189 spontaneous abortion cases, trisomy 16 was the most common numerical chromosome abnormality, followed by monosomy X. CNVs most often occurred on chromosomes 4 and 8. Gene Ontology and signaling pathway analysis revealed significant enrichment of genes related to nervous system development, transmembrane transport, cell adhesion, and structural components of chromatin. Furthermore, genes within the VOUS CNVs were screened by integrating human placental expression profiles, PhyloP scores, and Residual Variance Intolerance Score (RVIS) percentiles to identify potential candidate genes associated with spontaneous abortion. Fourteen potential candidate genes (LZTR1, TSHZ1, AMIGO2, H1-4, H2BC4, H2AC7, H3C8, H4C3, H3C6, PHKG2, PRR14, RNF40, SRCAP, ZNF629) were identified. Variations in LZTR1, TSHZ1, and H4C3 may contribute to embryonic lethality.

CONCLUSIONS

CNV sequencing (CNV-seq) analysis is an effective technique for detecting chromosomal abnormalities in POCs and identifying potential candidate genes for SA.

摘要

背景

自然流产（SA）的发生率约为15%-20%，是早期妊娠最常见的并发症。致病性拷贝数变异（CNV）被认为是SA的潜在遗传原因。然而，在妊娠产物（POC）中已鉴定出意义未明变异（VOUS）的CNV，其与SA的相关性仍不确定。

结果

在189例自然流产病例中，16三体是最常见的染色体数目异常，其次是X单体。CNV最常发生在4号和8号染色体上。基因本体论和信号通路分析显示，与神经系统发育、跨膜运输、细胞黏附及染色质结构成分相关的基因显著富集。此外，通过整合人胎盘表达谱、PhyloP评分和残余变异不耐受评分（RVIS）百分位数对VOUS CNV中的基因进行筛选，以鉴定与自然流产相关的潜在候选基因。共鉴定出14个潜在候选基因（LZTR1、TSHZ1、AMIGO2、H1-4、H2BC4、H2AC7、H3C8、H4C3、H3C6、PHKG2、PRR14、RNF40、SRCAP、ZNF629）。LZTR1、TSHZ1和H4C3的变异可能导致胚胎致死。