光学基因组图谱技术用于产前遗传学诊断的前瞻性研究。

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

机构信息

The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, China.

Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases, Ningbo Women and Children's Hospital, Ningbo, China.

出版信息

Clin Chem. 2024 Jun 3;70(6):820-829. doi: 10.1093/clinchem/hvae031.

DOI:10.1093/clinchem/hvae031

PMID:38517460

Abstract

BACKGROUND

Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis.

METHODS

A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed.

RESULTS

OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study.

CONCLUSIONS

Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

摘要

背景

光学基因组图谱（OGM）是一种检测结构变异（SV）的新型检测方法，其性能已被回顾性评估。然而，其在产前诊断中的前瞻性评估尚未见报道。本研究旨在前瞻性评估 OGM 与产前诊断中标准护理（SOC）检测的技术一致性。

方法

本研究纳入了 204 名孕妇的前瞻性队列。对这些孕妇的羊水样本进行 OGM 和 SOC 检测，包括染色体微阵列分析（CMA）和核型分析（KT）并行。评估 OGM 的诊断率，并评估 OGM 与 SOC 检测之间的技术一致性。

结果

OGM 成功分析了 204 个培养的羊水细胞样本，即使细胞计数低至 0.24 万。总共通过联合 OGM 和 SOC 检测鉴定出 60 个可报告的 SV，其中 22 个 SV 被 3 种技术全部检出。OGM、CMA 和 KT 的诊断率分别为 25%（51/204）、22.06%（45/204）和 18.14%（37/204）。当 OGM 和 KT 一起使用时，诊断率最高（29.41%，60/204）。在本队列研究中，OGM 与 CMA 的一致性为 95.56%，与 KT 的一致性为 75.68%。