학술논문
TREC/KREC Newborn Screening followed by Next-Generation Sequencing for Severe Combined Immunodeficiency in Japan.
Document Type
Article
Author
Wakamatsu, Manabu; Kojima, Daiei; Muramatsu, Hideki; Okuno, Yusuke; Kataoka, Shinsuke; Nakamura, Fumiko; Sakai, Yoshimi; Tsuge, Ikuya; Ito, Tsuyoshi; Ueda, Kazuto; Saito, Akiko; Morihana, Eiji; Ito, Yasuhiko; Ohashi, Naoki; Tanaka, Makito; Tanaka, Taihei; Kojima, Seiji; Nakajima, Yoko; Ito, Tetsuya; Takahashi, Yoshiyuki
Source
Subject
*SEVERE combined immunodeficiency
*NEWBORN screening
*NUCLEOTIDE sequencing
*DYSGENESIS
*T cell receptors
*PRIMARY immunodeficiency diseases
*GENETIC disorder diagnosis
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Language
ISSN
0271-9142
Abstract
Purpose: The aim of this study is to evaluate the usefulness of T cell receptor excision circle (TREC) and/or kappa-deleting recombination excision circle (KREC) measurements integrated with diagnostic next-generation sequencing (NGS) analysis using a severe combined immunodeficiency (SCID) newborn screening (NBS) program. Methods: TREC and/or KREC values were measured in 137,484 newborns between April 2017 and December 2021 using EnLite TREC (n = 80,791) or TREC/KREC kits (n = 56,693). For newborns with positive screening results, diagnostic NGS analysis was performed with a 349-gene panel to detect genetic mutations associated with primary immunodeficiencies (PIDs). Results: A total of 145 newborns (0.11%) had abnormal TREC and/or KREC values, and a genetic diagnosis was established in 2 patients with SCID (1 in 68,742 newborns) (IL2RG-SCID and reticular dysgenesis) and 10 with non-SCID PIDs with T and/or B cell deficiencies (1 in 13,748 newborns) using NGS analysis. Furthermore, TREC values of 2849 newborns were measured and confirmed the significant correlation between the results of both TREC and TREC/KREC kits (P < 0.001) and naïve T cell counts. Conclusions: We performed the first large-scale TREC and TREC/KREC NBS programs in Japan. Our NBS programs followed by the diagnostic NGS analysis for newborns with abnormal TREC and/or KREC values are useful for the early identification and rapid molecular evaluation of not only SCID but also different non-SCID PIDs. [ABSTRACT FROM AUTHOR]