Clinical, immunological and molecular findings of 8 patients with typical and atypical severe combined immunodeficiency: identification of 7 novel mutations by whole exome sequencing.
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
07
10
2022
accepted:
11
07
2023
revised:
04
07
2023
medline:
21
8
2023
pubmed:
30
7
2023
entrez:
29
7
2023
Statut:
ppublish
Résumé
Severe combined immunodeficiency (SCID) is one of the severe inborn errors of the immune system associated with life-threatening infections. Variations in SCID phenotypes, especially atypical SCID, may cause a significant delay in diagnosis. Therefore, SCID patients need to receive an early diagnosis. Here, we describe the clinical manifestations and genetic results of four SCID and atypical SCID patients. All patients (4 males and 4 females) in early infancy presented with SCID phenotypes within 6 months of birth. The mutations include RAG2 (p.I273T,p.G44X), IL7R (p.F361WfsTer17), ADA (c.780+1G>A), JAK3 (p.Q228Ter), LIG4 (p.G428R), and LAT (p.Y207fsTer33), as well as a previously reported missense mutation in RAG1 (p.A444V). The second report of LAT deficiency in SCID patients is presented in this study. Moreover, all variants were confirmed in patients and their parents as a heterozygous state by Sanger sequencing. The results of our study expand the clinical and molecular spectrum associated with SCID and leaky SCID phenotypes and provide valuable information for the clinical management of the patients.
Identifiants
pubmed: 37516813
doi: 10.1038/s41435-023-00215-w
pii: 10.1038/s41435-023-00215-w
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
207-214Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Ozturk E, Catak MC, Kiykim A, Baser D, Bilgic Eltan S, Yalcin K, et al. Clinical and laboratory factors affecting the prognosis of severe combined immunodeficiency. J Clin Immunol. 2022;42:1036–50.
doi: 10.1007/s10875-022-01262-0
pubmed: 35451701
Fischer A, Notarangelo LD, Neven B, Cavazzana M, Puck JM. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Prim. 2015;1:15061.
doi: 10.1038/nrdp.2015.61
pubmed: 27189259
Fazlollahi MR, Pourpak Z, Hamidieh AA, Movahedi M, Houshmand M, Badalzadeh M, et al. Clinical, laboratory, and molecular findings for 63 patients with severe combined immunodeficiency: a decade´s experience. J Investig Allergol Clin Immunol. 2017;27:299–304.
doi: 10.18176/jiaci.0147
pubmed: 28266921
Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A, et al. Clinical, immunological, and molecular features of typical and atypical severe combined immunodeficiency: report of the Italian primary immunodeficiency network. Front Immunol. 2019;10:1908.
doi: 10.3389/fimmu.2019.01908
pubmed: 31456805
pmcid: 6700292
Lim CK, Abolhassani H, Appelberg SK, Sundin M, Hammarstrom L. IL2RG hypomorphic mutation: identification of a novel pathogenic mutation in exon 8 and a review of the literature. Allergy Asthma Clin Immunol. 2019;15:2.
doi: 10.1186/s13223-018-0317-y
pubmed: 30622570
pmcid: 6320602
Cattaneo F, Recher M, Masneri S, Baxi SN, Fiorini C, Antonelli F, et al. Hypomorphic Janus kinase 3 mutations result in a spectrum of immune defects, including partial maternal T-cell engraftment. J Allergy Clin Immunol. 2013;131:1136–45.
doi: 10.1016/j.jaci.2012.12.667
pubmed: 23384681
pmcid: 6141242
Sundin M, Uhlin M, Gaballa A, Ramme K, Kolios AG, Marits P, et al. Late presenting atypical severe combined immunodeficiency (SCID) associated with a novel missense mutation in DCLRE1C. Pediatr Allergy Immunol. 2018;29:108–11.
doi: 10.1111/pai.12812
pubmed: 28981982
Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Bjorkman A, et al. DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency. Hum Mol Genet. 2015;24:7361–72.
doi: 10.1093/hmg/ddv437
pubmed: 26476407
pmcid: 4664172
Dvorak CC, Haddad E, Buckley RH, Cowan MJ, Logan B, Griffith LM, et al. The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018). J Allergy Clin Immunol. 2019;143:405–7.
doi: 10.1016/j.jaci.2018.08.027
pubmed: 30193840
Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, et al. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. Clin Immunol. 2011;141:73–82.
doi: 10.1016/j.clim.2011.05.007
pubmed: 21664875
Perez E. Future of therapy for inborn errors of immunity. Clin Rev Allergy Immunol. 2022;63:75–89.
doi: 10.1007/s12016-021-08916-8
pubmed: 35020169
pmcid: 8753954
Shearer WT, Dunn E, Notarangelo LD, Dvorak CC, Puck JM, Logan BR, et al. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol. 2014;133:1092–8.
doi: 10.1016/j.jaci.2013.09.044
pubmed: 24290292
Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J Clin Immunol. 2020;40:66–81.
doi: 10.1007/s10875-020-00758-x
pubmed: 32048120
pmcid: 7082388
Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Albarca Aguilera M, Meyer R, et al. VarSome: the human genomic variant search engine. Bioinformatics. 2018;35:1978–80.
doi: 10.1093/bioinformatics/bty897
pmcid: 6546127
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.
doi: 10.1038/gim.2015.30
pubmed: 25741868
pmcid: 4544753
Villa A, Sobacchi C, Notarangelo LD, Bozzi F, Abinun M, Abrahamsen TG, et al. V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood. 2001;97:81–8.
doi: 10.1182/blood.V97.1.81
pubmed: 11133745
Goda V, Malik A, Kalmar T, Maroti Z, Patel B, Ujhazi B, et al. Partial RAG deficiency in a patient with varicella infection, autoimmune cytopenia, and anticytokine antibodies. J Allergy Clin Immunol Pr. 2018;6:1769–71.e2.
doi: 10.1016/j.jaip.2018.01.015
McGrath-Morrow SA, Ndeh R, Helmin KA, Khuder B, Rothblum-Oviatt C, Collaco JM, et al. DNA methylation and gene expression signatures are associated with ataxia-telangiectasia phenotype. Sci Rep. 2020;10:7479.
doi: 10.1038/s41598-020-64514-2
pubmed: 32366930
pmcid: 7198504
Barata JT, Durum SK, Seddon B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol. 2019;20:1584–93.
doi: 10.1038/s41590-019-0479-x
pubmed: 31745336
Zhang W, Sommers CL, Burshtyn DN, Stebbins CC, DeJarnette JB, Trible RP, et al. Essential role of LAT in T cell development. Immunity. 1999;10:323–32.
doi: 10.1016/S1074-7613(00)80032-1
pubmed: 10204488
Zhang W, Irvin BJ, Trible RP, Abraham RT, Samelson LE. Functional analysis of LAT in TCR-mediated signaling pathways using a LAT-deficient Jurkat cell line. Int Immunol. 1999;11:943–50.
doi: 10.1093/intimm/11.6.943
pubmed: 10360968
Keller B, Zaidman I, Yousefi OS, Hershkovitz D, Stein J, Unger S, et al. Early onset combined immunodeficiency and autoimmunity in patients with loss-of-function mutation in LAT. J Exp Med. 2016;213:1185–99.
doi: 10.1084/jem.20151110
pubmed: 27242165
pmcid: 4925012
Bacchelli C, Moretti FA, Carmo M, Adams S, Stanescu HC, Pearce K, et al. Mutations in linker for activation of T cells (LAT) lead to a novel form of severe combined immunodeficiency. J Allergy Clin Immunol. 2017;139:634–42.e5.
doi: 10.1016/j.jaci.2016.05.036
pubmed: 27522155
Kuo CY, Garabedian E, Puck J, Cowan MJ, Sullivan KE, Buckley RH, et al. Adenosine deaminase (ADA)-deficient severe combined immune deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry. J Clin Immunol. 2020;40:1124–31.
doi: 10.1007/s10875-020-00857-9
pubmed: 32880085
pmcid: 8216639
Li M, Chen Z, Zhu Y, Chen J. Disseminated Bacille Calmette-Guérin infection in a patient with severe combined immunodeficiency caused by JAK3 gene mutation. Pediatr Dermatol. 2019;36:672–6.
doi: 10.1111/pde.13884
pubmed: 31309596
Stepensky P, Keller B, Shamriz O, NaserEddin A, Rumman N, Weintraub M, et al. Deep intronic mis-splicing mutation in JAK3 gene underlies T-B+NK- severe combined immunodeficiency phenotype. Clin Immunol. 2016;163:91–5.
doi: 10.1016/j.clim.2016.01.001
pubmed: 26769277
El Hawary R, Meshaal S, Mauracher AA, Opitz L, Abd Elaziz D, Lotfy S, et al. Whole-exome sequencing of T(-) B(+) severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants. Clin Exp Immunol. 2021;203:448–57.
doi: 10.1111/cei.13536
pubmed: 33040328
Qamar F, Junejo S, Qureshi S, Seleman M, Bainter W, Massaad M, et al. A novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis. Clin Immunol. 2017;183:198–200.
doi: 10.1016/j.clim.2017.09.007
pubmed: 28917720
Sun B, Chen Q, Wang Y, Liu D, Hou J, Wang W, et al. LIG4 syndrome: clinical and molecular characterization in a Chinese cohort. Orphanet J Rare Dis. 2020;15:131.
doi: 10.1186/s13023-020-01411-x
pubmed: 32471509
pmcid: 7257218
Altmann T, Gennery AR. DNA ligase IV syndrome; a review. Orphanet J Rare Dis. 2016;11:137.
doi: 10.1186/s13023-016-0520-1
pubmed: 27717373
pmcid: 5055698
Felgentreff K, Baxi SN, Lee YN, Dobbs K, Henderson LA, Csomos K, et al. Ligase-4 deficiency causes distinctive immune abnormalities in asymptomatic individuals. J Clin Immunol. 2016;36:341–53.
doi: 10.1007/s10875-016-0266-5
pubmed: 27063650
pmcid: 4842108
Taskiran EZ, Sonmez HE, Kosukcu C, Tavukcuoglu E, Yazici G, Esendagli G, et al. A novel missense LIG4 mutation in a patient with a phenotype mimicking Behçet’s disease. J Clin Immunol. 2019;39:99–105.
doi: 10.1007/s10875-018-0587-7
pubmed: 30617623
Taki M, Miah T, Secord E. Newborn screening for severe combined immunodeficiency. Pediatr Clin North Am. 2019;66:913–23.
doi: 10.1016/j.pcl.2019.06.007
pubmed: 31466681
Cuvelier GDE, Logan BR, Prockop SE, Buckley RH, Kuo CY, Griffith LM, et al. Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC. Blood. 2022;140:685–705.
doi: 10.1182/blood.2022016196
pubmed: 35671392