Mutational landscape of severe combined immunodeficiency patients from Turkey.

Adenosine Deaminase / genetics Adolescent Adult Alleles B-Lymphocytes / immunology CD3 Complex / genetics Child, Preschool DNA Mutational Analysis DNA Repair Enzymes / genetics DNA-Binding Proteins / genetics Endonucleases / genetics Female Genetic Variation High-Throughput Nucleotide Sequencing Homeodomain Proteins / genetics Humans Infant Infant, Newborn Interleukin Receptor Common gamma Subunit / genetics Interleukin-7 Receptor alpha Subunit / genetics Janus Kinase 3 / genetics Killer Cells, Natural / immunology Male Mutation Nuclear Proteins / genetics Phenotype Prognosis Severe Combined Immunodeficiency / genetics T-Lymphocytes / immunology Turkey / epidemiology

Primary immunodeficiency SCID targeted next-generation sequencing

Journal

International journal of immunogenetics

ISSN: 1744-313X

Titre abrégé: Int J Immunogenet

Pays: England

ID NLM: 101232337

Informations de publication

Date de publication:
Dec 2020

Historique:

received: 09 12 2019

revised: 06 04 2020

accepted: 30 04 2020

pubmed: 24 5 2020

medline: 16 6 2021

entrez: 24 5 2020

Statut: ppublish

Résumé

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy.

Identifiants

DOI: 10.1111/iji.12496 PMID: 32445296

pubmed: 32445296

doi: 10.1111/iji.12496

doi:

Substances chimiques

CD3 Complex 0

CD3E protein, human 0

DNA-Binding Proteins 0

Homeodomain Proteins 0

IL2RG protein, human 0

IL7R protein, human 0

Interleukin Receptor Common gamma Subunit 0

Interleukin-7 Receptor alpha Subunit 0

NHEJ1 protein, human 0

Nuclear Proteins 0

RAG2 protein, human 0

RAG-1 protein 128559-51-3

JAK3 protein, human EC 2.7.10.2

Janus Kinase 3 EC 2.7.10.2

DCLRE1C protein, human EC 3.1.-

Endonucleases EC 3.1.-

ADA protein, human EC 3.5.4.4

Adenosine Deaminase EC 3.5.4.4

DNA Repair Enzymes EC 6.5.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

529-538

Subventions

Organisme : Istanbul Bilgi University

ID : NGYY-2018.01.0006

Organisme : Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi

ID : 52575

Organisme : Bilimsel Araştirma Projeleri Birimi, Istanbul Üniversitesi

ID : 20499

Informations de copyright

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