Identification and prenatal diagnosis for a novel NIPBL variant in a fetus with Cornelia de Lange syndrome
10.3760/cma.j.cn511374-20230517-00294
- VernacularTitle:德朗热综合征1例胎儿的 NIPBL基因变异鉴定及产前诊断
- Author:
Yan ZHAO
1
;
Shan SHAN
;
Kaihua ZHANG
;
Hua JIN
;
Fei HOU
;
Luquan CAO
Author Information
1. 山东第一医科大学附属济南妇幼保健院（济南市妇幼保健院）产前诊断中心，济南 250001
- Keywords:
Cornelia de Lange syndrome;
NIPBL gene;
Prenatal diagnosis
- From:
Chinese Journal of Medical Genetics
2024;41(7):835-839
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a fetus with nuchal cystic hygroma identified in the first trimester and cholecystomegaly identified in the middle trimester of pregnancy.Methods:A 27-year-old pregnant woman who had presented at the Antenatal Diagnostic Center of Jinan Maternal and Child Health Care Hospital on October 25, 2018 was selected as the study subject. Chorionic villus sampling was carried out in the first trimester for chromosomal karyotyping and SNP-Array analysis. Amniocentesis was carried out in the second trimester, and peripheral blood of the couple was collected at the same time. Trio whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:No abnormality was found by chromosomal karyotyping and SNP-Array, whilst high-throughput sequencing revealed that the fetus had harbored a heterozygous c. 7732A>T (p.K2578X) nonsense variant of the NIPBL gene. Following elected abortion, the autopsy results were consistent with features of Cornelia de Lange syndrome (CdLS). The same variant was detected in neither parents and was unreported in the literature. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as pathogenic (PVS1+ PS2+ PM2_Supporting+ PP3). Conclusion:The novel nonsense variant of the NIPBL gene probably underlay the genetic etiology of CdLS in this fetus. Above finding has also enriched the mutational spectrum of the NIPBL gene.
