| Autor: |
Zhang JY; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Chen SC; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Chen YY; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Li SY; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Zhang LL; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Shen YH; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Chang CX; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Xiang YQ; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Huang HF; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China., Xu CM; The International Peace Maternity & Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.; Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China. |
| Abstrakt: |
X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immunodeficiency characterized by a clinical triad consisting of severe EBV-induced hemophagocytic lymphohistiocytosis, B-cell lymphoma, and dysgammaglobulinemia. Mutations in SH2D1A gene have been revealed as the cause of XLP1. In this study, a pregnant woman with recurrence history of birthing immunodeficiency was screened for pathogenic variant because the proband sample was unavailable. We aimed to clarify the genetic diagnosis and provide prenatal testing for the family. Next-generation sequencing (NGS)-based multigene panel was used in carrier screening of the pregnant woman. Variants of immunodeficiency related genes were analyzed and prioritized. Candidate variant was verified by using Sanger sequencing. The possible influence of the identified variant was evaluated through RNA assay. Amniocentesis, karyotyping, and Sanger sequencing were performed for prenatal testing. We identified a novel de novo frameshift SH2D1A pathogenic variant (c.251_255delTTTCA) in the pregnant carrier. Peripheral blood RNA assay indicated that the mutant transcript could escape nonsense-mediated mRNA decay (NMD) and might encode a C-terminal truncated protein. Information of the variant led to success prenatal diagnosis of the fetus. In conclusion, our study clarified the genetic diagnosis and altered disease prevention for a pregnant carrier of XLP1. |
