胼胝体发育不全的胎儿：40 例患者的临床和遗传学分析。

Fetal agenesis of the corpus callosum: Clinical and genetic analysis in a series of 40 patients.

机构信息

Department of Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Department of Ultrasound, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2024 Jul;298:146-152. doi: 10.1016/j.ejogrb.2024.05.005. Epub 2024 May 8.

DOI:10.1016/j.ejogrb.2024.05.005

PMID:38756055

Abstract

OBJECTIVES

This study aimed to explore the genetic causes of agenesis of the corpus callosum (ACC) and assess the utility of karyotype analysis, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) to genetically diagnose fetal ACC.

METHODS

We retrospectively examined 40 fetuses diagnosed with ACC who underwent prenatal ultrasonography or magnetic resonance imaging between January 2019 and October 2023. Genetic tests were conducted on the fetuses using karyotype analysis or CNV-seq as the first-line diagnosis. WES was performed if aneuploid and pathogenic CNVs were excluded.

RESULTS

Among the 40 fetuses, 29 (72 %) had non-isolated ACC and 11 (28 %) had isolated ACC. Cerebellar dysplasia and hydrocephalus were the most common abnormal developments in the central nervous system. Twenty-eight patients underwent karyotype analysis, with a detection rate of 14 % (4/28). Twenty-six patients underwent CNV-seq; three patients were found to have pathogenic CNVs, with a detection rate of 12 % (3/26). Thirty-three fetuses with no findings of karyotype analysis or CNV-seq were subsequently tested using WES, with a detection rate of 36 % (12/33). Overall, the total diagnostic yield was 48 % (19/40), and monogenic etiology accounted for 30 % (12/40). The genetic detection rate of fetal non-isolated ACC (62 %, 18/29) was higher than that of isolated ACC (9 %, 1/11).

CONCLUSION

Prenatal genetic analysis of fetuses with ACC is clinically significant, with monogenic disorders being the main cause. WES may enhance the detection rate of fetuses with ACC with negative karyotype analysis or CNV-seq results.

摘要

目的

本研究旨在探讨胼胝体发育不全（ACC）的遗传病因，并评估核型分析、拷贝数变异测序（CNV-seq）和全外显子组测序（WES）在遗传诊断胎儿 ACC 中的应用价值。

方法

我们回顾性分析了 2019 年 1 月至 2023 年 10 月期间因产前超声或磁共振成像诊断为 ACC 的 40 例胎儿。对胎儿进行核型分析或 CNV-seq 作为一线诊断，如果排除非整倍体和致病性 CNVs，则进行 WES。

结果

在 40 例胎儿中，29 例（72%）为非孤立性 ACC，11 例（28%）为孤立性 ACC。小脑发育不良和脑积水是中枢神经系统最常见的异常发育。28 例患者进行了核型分析，检出率为 14%（4/28）。26 例患者进行了 CNV-seq；发现 3 例存在致病性 CNVs，检出率为 12%（3/26）。33 例核型分析或 CNV-seq 无发现的胎儿随后进行了 WES 检测，检出率为 36%（12/33）。总体而言，总诊断率为 48%（19/40），单基因病因占 30%（12/40）。胎儿非孤立性 ACC 的遗传检出率（62%，18/29）高于孤立性 ACC（9%，1/11）。