Clinical and Immunological Heterogeneity in Japanese Patients with Gain-of-Function Variants in STAT3.
J Clin Immunol
; 41(4): 780-790, 2021 05.
Article
en En
| MEDLINE
| ID: mdl-33501615
ABSTRACT
PURPOSE:
Germline loss-of-function variants in the signal transducer and activator of transcription 3 (STAT3) gene result in autosomal dominant hyper IgE syndrome, whereas somatic gain-of-function (GOF) variants in STAT3 are associated with some malignancies. In addition, germline GOF variants in STAT3 are linked to disorders involving autoimmunity and lymphoproliferation. In this study, we describe five Japanese families with germline GOF variants in STAT3, including three novel variants. We also present the clinical and immunological characteristics of these patients.METHODS:
Eight patients from five families were enrolled in this study. We performed genetic and immunological analyses, and collected the associated clinical information.RESULTS:
We identified five heterozygous variants in STAT3 using whole-exome sequencing and target gene sequencing. Two of these (E286G and T716M) were previously reported and three (K348E, E415G, and G618A) were novel. A STAT3 reporter assay revealed that all of the variants were GOF. However, the immunological and clinical characteristics among the patients were highly variable.CONCLUSION:
Patients with STAT3 GOF variants exhibited clinical and immunological heterogeneity with incomplete penetrance.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Factor de Transcripción STAT3
/
Mutación con Ganancia de Función
/
Variación Biológica Poblacional
/
Enfermedades del Sistema Inmune
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Clin Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón