Genetic analysis of two fetuses with Mosaic variegated aneuploidy syndrome caused by compound heterozygous variants in BUB1B and its upstream regulatory elements and a literature review
10.3760/cma.j.cn511374-20240716-00393
- VernacularTitle:BUB1B基因内及上游调控子位点复合杂合变异致嵌合性杂色非整倍体综合征2例胎儿的遗传学分析暨文献综述
- Author:
Jiangbo QU
1
;
Wenjuan ZHU
;
Ju WANG
;
Lu GAO
;
Dongyi YU
Author Information
1. 青岛大学附属山东省妇幼保健院医学遗传与产前诊断中心（山东省医药卫生出生缺陷防治与遗传医学重点实验室，国家卫生健康委员会母胎医学重点实验室），济南 250014
- Publication Type:Journal Article
- Keywords:
BUB1B gene;
Mosaic variegated aneuploidy syndrome;
Polymorphism, Single Nucleotide;
Whole exome sequencing;
Fetus
- From:
Chinese Journal of Medical Genetics
2025;42(4):446-453
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree.Methods:A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034).Results:① Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. ② WES identified compound heterozygous variants in BUB1B — c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A — in both fetuses. Sanger sequencing confirmed paternal inheritance of c. 2363_2364del and maternal inheritance of ss804270619: G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource(ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c. 2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. Conclusion:The compound heterozygous variants c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.
