Application of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency
10.3760/cma.j.cn511374-20221220-00879
- VernacularTitle:全外显子组测序在有免疫缺陷患儿夭折史夫妻双方隐性遗传病携带情况推断分析中的应用
- Author:
Bing ZHANG
1
;
Ke YANG
;
Yuwei ZHANG
;
Guiyu LOU
;
Na QI
;
Xingxing LEI
;
Fengyang WANG
;
Bing KANG
;
Shixiu LIAO
Author Information
1. 河南省人民医院/河南省人民医院医学遗传研究所，郑州 450003
- Keywords:
Immunodeficiency;
Whole exome sequencing;
Variant;
Recessive disorder
- From:
Chinese Journal of Medical Genetics
2024;41(2):134-139
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID).Methods:Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People′s Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants.Results:A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c. 676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c. 184_185delAC variant of the BTK gene, and the c. 472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c. 184_185delAC and CYBB: c. 472A>T variants were classified as likely pathogenic (PVS1+ PM2_Supporting+ PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c. 184_185 position of the BTK gene, the c. 472 position of the CYBB gene, and the c. 676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. Conclusion:WES is an important tool to infer and analyze the carryier status for couples who had given births to children died of PID and improve the positive detection rate.
