Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal guthrie cards.
OBJECTIVE
To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID).


METHODS
Real-time PCR based quantification of TRECs for 471 healthy control patients and 18 patients with SCID with various genetic abnormalities (IL2RG, JAK3, ADA, LIG4, RAG1) were performed, including patients with maternal T-cell engraftment (n = 4) and leaky T cells (n = 3).


RESULTS
TRECs were detectable in all normal neonatal Guthrie cards (n = 326) at the levels of 10(4) to 10(5) copies/microg DNA. In contrast, TRECs were extremely low in all neonatal Guthrie cards (n = 15) and peripheral blood (n = 14) from patients with SCID, including those with maternal T-cell engraftment or leaky T cells with hypomorphic RAG1 mutations or LIG4 deficiency. There were no false-positive or negative results in this study.


CONCLUSIONS
TRECs quantification can be used as a neonatal mass screening for patients with SCID.
Morinishi
Yoichi
Y
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
Imai
Kohsuke
K
Nakagawa
Noriko
N
Sato
Hiroki
H
Horiuchi
Katsuyuki
K
Ohtsuka
Yoshitoshi
Y
Kaneda
Yumi
Y
Taga
Takashi
T
Hisakawa
Hiroaki
H
Miyaji
Ryosuke
R
Endo
Mikiya
M
Oh-Ishi
Tsutomu
T
Kamachi
Yoshiro
Y
Akahane
Koshi
K
Kobayashi
Chie
C
Tsuchida
Masahiro
M
Morio
Tomohiro
T
Sasahara
Yoji
Y
Kumaki
Satoru
S
Ishigaki
Keiko
K
Yoshida
Makoto
M
Urabe
Tomonari
T
Kobayashi
Norimoto
N
Okimoto
Yuri
Y
Reichenbach
Janine
J
Hashii
Yoshiko
Y
Tsuji
Yoichiro
Y
Kogawa
Kazuhiro
K
Yamaguchi
Seiji
S
Kanegane
Hirokazu
H
Miyawaki
Toshio
T
Yamada
Masafumi
M
Ariga
Tadashi
T
Nonoyama
Shigeaki
S
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D015997:Neonatal Screening / Q000379:methods*; D011237:Predictive Value of Tests; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043262:Ribonuclease P / Q000097:blood; D016511:Severe Combined Immunodeficiency / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
D011948:Receptors, Antigen, T-Cell; D043262:Ribonuclease P