Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis.
J Clin Immunol
; 35(7): 598-603, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26399252
ABSTRACT
ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a total of 13 cases. Here we report a novel homozygous 10 base pair frameshift deletion in exon 2 discovered by whole exome sequencing of two siblings from a family of Pakistani origin. Both patients presented in early childhood with diarrhea, colitis and transaminitis and one showed defective handling of human herpesvirus 6. Activated patient CD3(+)CD4(+) T lymphocytes demonstrated a complete absence of ICOS expression and, consistent with previous reports, we detected a reduction in circulating T follicular helper cells. Findings in this kindred emphasise the phenotypic variability of ICOS deficiency and, in particular, the variably impaired antiviral immunity that is a poorly understood facet of this rare disorder.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Colaboradores-Inductores
/
Herpesvirus Humano 6
/
Infecciones por Roseolovirus
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Enteritis
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Proteína Coestimuladora de Linfocitos T Inducibles
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Hepatitis
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Síndromes de Inmunodeficiencia
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Clin Immunol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Reino Unido