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Mutational landscape of severe combined immunodeficiency patients from Turkey
Author(s) -
Firtina Sinem,
Yin Ng Yuk,
Hatirnaz Ng Ozden,
Kiykim Ayca,
Aydiner Elif,
Nepesov Serdar,
Camcioglu Yildiz,
Sayar Esra H.,
Reisli Ismail,
Torun Selda H.,
Cogurlu Tuba,
Uygun Dilara,
Simsek Isil E.,
Kaya Aysenur,
Cipe Funda,
Cagdas Deniz,
Yucel Esra,
Cekic Sukru,
Uygun Vedat,
Baris Safa,
Ozen Ahmet,
Ozbek Ugur,
Sayitoglu Muge
Publication year - 2020
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/iji.12496
Subject(s) - severe combined immunodeficiency , recombination activating gene , rag2 , etiology , gene , biology , immunodeficiency , genetics , medicine , immune system , recombination
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.