A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant.
J Clin Immunol
; 39(4): 430-439, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-31079270
ABSTRACT
PURPOSE:
This study aimed to characterize the clinical phenotype, genetic basis, and consequent immunological phenotype of a boy with severe infantile-onset colitis and eosinophilic gastrointestinal disease, and no evidence of recurrent or severe infections.METHODS:
Trio whole-exome sequencing (WES) was utilized for pathogenic variant discovery. Western blot (WB) and immunohistochemical (IHC) staining were used for protein expression analyses. Immunological workup included in vitro T cell studies, flow cytometry, and CyTOF analysis.RESULTS:
WES revealed a homozygous variant in the capping protein regulator and myosin 1 linker 2 (CARMIL2) gene c.1590C>A; p.Asn530Lys which co-segregated with the disease in the nuclear family. WB and IHC analyses demonstrated reduced protein levels in patient's cells compared with controls. Moreover, comprehensive immunological workup revealed severely diminished blood-borne regulatory T cell (Treg) frequency and impaired in vitro CD4+ T cell proliferation and Treg generation. CyTOF analysis showed significant shifts in the patient's innate and adaptive immune cells compared with healthy controls and ulcerative colitis patients.CONCLUSIONS:
Pathogenic variants in CARMIL2 have been implicated in an immunodeficiency syndrome characterized by recurrent infections, occasionally with concurrent chronic diarrhea. We show that CARMIL2-immunodeficiency is associated with significant alterations in the landscape of immune populations in a patient with prominent gastrointestinal disease. This case provides evidence that CARMIL2 should be a candidate gene when diagnosing children with very early onset inflammatory and eosinophilic gastrointestinal disorders, even when signs of immunodeficiency are not observed.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Colite
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Enterite
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Eosinofilia
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Gastrite
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Homozigoto
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Proteínas dos Microfilamentos
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Child
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Child, preschool
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article