Pedigree analysis and prenatal diagnosis of intellectual disability caused by synonymous mutations of p.S434S in DLG3 gene
10.3760/cma.j.cn113903-20210820-00712
- VernacularTitle:DLG3基因p.S434S同义变异致智力障碍家系分析及产前诊断1例
- Author:
Jia HUANG
1
;
Hongjie ZHU
;
Jiahuan HE
;
Xi LI
;
Xingxing LEI
;
Hongdan WANG
;
Congmin LI
;
Yue WANG
;
Hongyan LIU
Author Information
1. 郑州大学人民医院 河南省人民医院医学遗传研究所，郑州 450003
- Keywords:
Intellectual disability;
Nuclear proteins;
Transcription factors;
Silent mutation;
Whole exome sequencing;
Prenatal diagnosis
- From:
Chinese Journal of Perinatal Medicine
2022;25(1):42-47
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the pathogenic gene and prenatal diagnosis of a family with intellectual disability.Methods:Out of this family consisting of 17 members in three generations, four males had intellectual disability. The proband's elder sister (Ⅱ-7) visited Henan Provincial People's Hospital in Oct 2019 for genetic counseling at 8 weeks of gestation. After informed consent was obtained, peripheral blood samples of the family members were collected. The whole exome sequencing was performed on the genome DNA of the proband (Ⅱ-9, male) and his parents to screen the candidate variants for phenotype co-segregated analysis by Sanger sequencing. The expression vectors were constructed by homologous recombination and the splicing experiments were performed in vitro. Reverse transcription polymerase chain reaction, Sanger sequencing, and TA clone sequencing were used to analyze the effect of candidate variants on splicing. After the pathogenic variant was determined the proband's elder sister underwent prenatal diagnosis (Ⅲ-7) using goldeneyeTM20A genotyping system and Sanger sequencing. Results:A hemizygous synonymous variant of c.1302G>A (p. S434S) in DLG3 gene was found in the proband by whole exome sequencing, which was carried by his mother (Ⅰ-1) and co-segregated with the phenotype in other family patients. In vitro splicing experiment showed that c.1302G>A variant led to abnormal splicing of 88.24% transcripts, which further resulted in the reading frame shift and protein function impairment. The mutation was not detected in the fetus (Ⅲ-7), who was born alive later and showed no abnormal mental or behavioral development at the age of one and a half year and is still being followed up. Conclusions:The synonymous mutation c.1302G>A in DLG3 gene was the etiopathogenesis of X-linked intellectual disability in this family.
