Genetic analysis of a pregnant woman with moderate intellectual disability due to variant of DLG4 gene.
10.3760/cma.j.cn511374-20221114-00786
- VernacularTitle:DLG4基因变异导致中度智力低下孕妇1例的遗传学分析
- Author:
Panla SHI
1
;
Xuechao ZHAO
;
Li'na LIU
;
Yanjie XIA
;
Conghui WANG
;
Duo CHEN
;
Yaqin HOU
;
Zhouxian BAI
;
Xiangdong KONG
Author Information
1. Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. kongxd@263.net.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Pregnancy;
Young Adult;
Disks Large Homolog 4 Protein;
DNA Copy Number Variations;
Fetus;
Genetic Testing;
Intellectual Disability/genetics*;
Pregnant Women
- From:
Chinese Journal of Medical Genetics
2023;40(3):354-359
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID).
METHODS:The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs.
RESULTS:The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA.
CONCLUSION:The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.
