Genetic analysis of a fetus with Cornelia de Lange syndrome due to variant of SMC3 gene
10.3760/cma.j.cn511374-20230116-00029
- VernacularTitle:SMC3基因变异致德朗热综合征1例胎儿的遗传学分析
- Author:
Hui HUANG
1
;
Peiwen CHEN
;
Qian FENG
;
Ya LIU
;
Chen CHENG
;
Xinlin CHEN
Author Information
1. 湖北省妇幼保健院超声诊断科，武汉 430070
- Keywords:
Cornelia de Lange syndrome;
SMC3 gene;
Whole exome sequencing;
Sanger sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(2):250-254
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic basis for a fetus featuring oligodactyly.Methods:A fetus with hand deformity identified by ultrasound at the Maternal and Child Health Care Hospital of Hubei Province on October 20, 2018 was selected as the study subject. Clinical information and ultrasonographic finding of the pregnant woman were collected. Following elected abortion, umbilical cord and peripheral venous blood samples of the couple were collected for the extraction of genomic DNA. Copy number variation sequencing (CNV-seq) and trio-whole exome sequencing (trio-WES) were carried out. Candidate variants were verified by Sanger sequencing.Results:Ultrasonographic examination at 30 + 2 weeks of gestation revealed that the fetus had small right hand with absence of 2nd ~ 5th fingers, whilst its left hand had appeared to be normal. By CNV-seq, no pathogenic or likely pathogenic copy number variation (CNV) (> 100 kb) was detected in the fetus. Trio-WES revealed that the fetus had harbored a novel heterozygous c.3298G>A (p.Val1100Met) variant of the SMC3 gene. The variant has not been recorded in the population databases, and was predicted to be deleterious by several bioinformatics software and evolutionarily conserved based on multiple sequence alignment analysis. Sanger sequencing showed that neither parent has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS2+ PM2_Supporting+ PP3). Conclusion:The fetus was diagnosed with Cornelia de Lange syndrome, for which the novel heterozygous c.3298G>A variant of the SMC3 gene may be accountable.
