1. Targeted sequencing identifies a novel SH2D1A pathogenic variant in a Chinese family: Carrier screening and prenatal genetic testing
- Author
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Jun-Yu Zhang, Chenming Xu, Songchang Chen, Yu-Qian Xiang, Yinghua Shen, He-Feng Huang, Chunxin Chang, Yiyao Chen, Lanlan Zhang, and Shuyuan Li
- Subjects
Male ,0301 basic medicine ,Proband ,Genetic Screens ,Molecular biology ,Maternal Health ,Gene Identification and Analysis ,lcsh:Medicine ,Artificial Gene Amplification and Extension ,Biochemistry ,Polymerase Chain Reaction ,Sequencing techniques ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,Medicine and Health Sciences ,DNA sequencing ,Signaling Lymphocytic Activation Molecule Associated Protein ,Frameshift Mutation ,lcsh:Science ,Immunodeficiency ,Sanger sequencing ,Genetics ,Multidisciplinary ,medicine.diagnostic_test ,Messenger RNA ,Obstetrics and Gynecology ,High-Throughput Nucleotide Sequencing ,Genomics ,Pedigree ,Nucleic acids ,030220 oncology & carcinogenesis ,Amniocentesis ,symbols ,Female ,Research Article ,Adult ,Immunology ,Prenatal diagnosis ,Frameshift mutation ,Immune Deficiency ,03 medical and health sciences ,symbols.namesake ,Genomic Medicine ,Diagnostic Medicine ,medicine ,Humans ,Genetic Testing ,RNA, Messenger ,Genetic testing ,Clinical Genetics ,business.industry ,lcsh:R ,Dideoxy DNA sequencing ,Biology and Life Sciences ,Human Genetics ,Reverse Transcriptase-Polymerase Chain Reaction ,medicine.disease ,Lymphoproliferative Disorders ,Nonsense Mediated mRNA Decay ,Research and analysis methods ,Molecular biology techniques ,030104 developmental biology ,Mutation ,Primary immunodeficiency ,Women's Health ,RNA ,Clinical Immunology ,lcsh:Q ,Clinical Medicine ,business - Abstract
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.
- Published
- 2017