早发型严重胎儿生长受限的产前与产后遗传学检测结果
该回顾性研究纳入40例32周前诊断的孤立性严重胎儿生长受限单胎妊娠，评估核型分析与染色体微阵列（CMA）的诊断率，部分病例行外显子/基因组测序。CMA诊断2/39（5.1%），致病性CNV涉及SHOX基因及母源UPD6，10%病例检出≥1个>10Mb的纯合区域（AOH）。
要点
- 32周前孤立性严重FGR中CMA诊断率为5.1%（2/39）。
- 10%病例检出>10Mb的AOH，提示需进一步研究其与FGR的关联。
- 核型分析（27/40）均正常，测序（N=10）仅检出1例COL1A1的VUS。
核心结论
- CMA在早发型孤立性严重FGR中诊断率为2/39（5.1%），检出致病性CNV涉及SHOX基因及母源UPD6，均与FGR一致。
- AOH发生率高达10%，需进一步研究其是否为FGR的 contributing factor。
研究设计与样本
- 回顾性研究纳入2022-2025年分娩的单胎妊娠，胎估体重或腹围<第3百分位且孕周<32周，无超声结构异常，行羊膜腔穿刺或脐血诊断性检测（核型、CMA、ES或GS）。
- 排除游离DNA异常病例，共40例，平均诊断孕周26.8周；羊膜腔穿刺占42%，脐血占58%。
主要发现
- 核型分析（27/40）均正常。
- CMA（39/40）检出1例致病性CNV（2.5%）和3例（7.5%）意义不明变异（VUS）。
- 4例（10%）检出≥1个>10Mb的AOH区域，其中1例为6号染色体母源单亲二体。
- 测序（N=10）检出1例COL1A1的VUS。
- 所有病例均未观察到急性病毒感染。
关键数值与推荐
- CMA诊断2/39（5.1%）：1例致病性CNV涉及SHOX基因，1例母源UPD6。
- VUS检出3/39（7.5%），AOH（>10Mb）检出4/40（10%）。
临床怎么用
- 对32周前诊断的孤立性严重FGR，CMA可作为一线遗传学检测手段。
- 检出AOH时需考虑单亲二体可能，并咨询进一步胎盘研究和基因组测序的必要性。
局限性
- 回顾性设计，样本量较小（40例），测序仅10例。
- AOH与FGR的因果关系未明确，需进一步研究。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVES: We evaluated the diagnostic yield of karyotype (KT) and chromosomal microarray (CMA) with isolated severe FGR diagnosed before 32 weeks' gestation. Exome and genome sequencing (ES/GS) level data were available in a subset of this population. METHOD: We performed a retrospective review of singleton pregnancies (delivered 2022-2025) with estimated fetal weight or abdominal circumference < 3rd percentile before 32 weeks' gestation, no sonographic structural anomalies, and diagnostic testing (KT, CMA, ES, or GS) via amniocentesis or cord blood. Cases with abnormal cell-free DNA were excluded. RESULTS: Forty cases were included (mean diagnosis 26.8 weeks). Testing was performed via amniocentesis in 42% and cord blood in 58%. All KT (27/40) were normal. CMA (39/40) identified one pathogenic CNV (2.5%) and three (7.5%) variants of uncertain significance (VUS). Four (10%) showed ≥ 1 region of absence of heterozygosity (AOH) > 10Mb; one revealed maternal uniparental disomy of chromosome 6. Sequencing (N = 10) detected one VUS in COL1A1. Acute viral infection was not observed in any of the cases. CONCLUSIONS: CMA was diagnostic in 2/39 (5.1%) cases, a pathogenic CNV implicating the SHOX gene, and maternal UPD 6, which were consistent with FGR. There was a remarkable rate (10%) of AOH. Further investigation, including placental studies and genome sequencing, may elucidate whether AOH is a contributing factor for FGR.
引用
- Mossayebi MH, Adams SJ, Bunnell ME, et al. Severe Early-Onset Fetal Growth Restriction: The Yield of Antenatal and Postnatal Genetic Testing. Prenat Diagn. 2026. PMID: 42153347. doi:10.1002/pd.70182
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。