Related Experiment Video

Updated: May 12, 2026

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

BENTA disease or CARD11 gain-of-function? A novel variant with atypical features and a literature review

Letizia Baldini1, Bärbel Keller2, Lisa Dewitte3

  • 1Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; Dipartimento di Scienza della Sanità Pubblica e Pediatriche, Università degli Studi di Torino, Torino, Italy.

Immunology Letters
|March 29, 2025
PubMed

Insights

Gain-of-function mutations in the CARD11 gene cause BENTA disease. A novel CARD11 mutation presents atypically and highlights the risk of Hemophagocytic Lymphohistiocytosis (HLH) in these disorders.

Area of Science:

  • Immunology
  • Genetics
  • Molecular Biology

Background:

  • CARD11 (Caspase Recruitment Domain Family Member 11) is crucial for NF-κB signaling and immune cell function.
  • Gain-of-function (GOF) mutations in CARD11 lead to BENTA disease, characterized by B-cell expansion, immune dysfunction, and infections.

Purpose of the Study:

  • To describe a novel CARD11-GOF mutation (D357E) and its associated atypical BENTA phenotype.
  • To expand the understanding of the clinical spectrum of CARD11-GOF disorders.
  • To assess the prevalence of Hemophagocytic Lymphohistiocytosis (HLH) in CARD11-GOF mutations.

Main Methods:

  • Clinical description of three patients with a novel CARD11-GOF mutation (D357E).
  • In vitro functional analysis of the D357E variant's effect on NF-κB signaling.
  • Systematic literature review of CARD11 GOF mutations using PubMed and EMBASE.

Main Results:

  • The novel D357E variant activates NF-κB signaling in lymphocytes and HEK293T cells.
  • Atypical BENTA phenotype observed, including high IgM and normal B-cell counts; one patient developed life-threatening HLH.
  • Literature review of 29 patients revealed HLH as a common complication (18.8%), not always accompanied by B-lymphocytosis.

Conclusions:

  • A novel pathogenic CARD11 variant expands the known clinical spectrum of CARD11 GOF disorders.
  • Increased awareness of HLH risk is crucial for patients with CARD11 GOF mutations.
  • The findings emphasize the variable clinical presentation of BENTA disease.
Abstract

Keywords:
BENTA diseaseCARD11HLH

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Related Concept Videos

Pedigree Analysis01:35

Pedigree Analysis

Overview
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Incomplete Dominance01:43

Incomplete Dominance

Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...