CARD9 mutations in patients with fungal infections: An update from the last 5 years

Area of Science:

• Immunology
• Medical Genetics
• Infectious Diseases

Background:

• Autosomal recessive deficiency in caspase recruitment domain-containing protein 9 (CARD9) predisposes individuals to fungal infections.
• There is a rising incidence and recognition of fungal infections in patients with CARD9 deficiency.

Purpose of the Study:

• To investigate the frequency, geographic distribution, and nature of mutations in the CARD9 gene in patients with CARD9 deficiency.
• To correlate specific CARD9 mutations with particular fungal infection types and geographical prevalence.

Main Methods:

• Systematic literature review of case reports from October 2009 to March 2023.
• Data extraction from PubMed, Embase, Scopus, and Google Scholar databases.
• Analysis of 90 documented cases of fungal infections associated with CARD9 deficiency.

Main Results:

• Thirty-two distinct mutations in the CARD9 gene were identified across 90 cases.
• Homozygous p.Q295X mutation is linked to increased candidiasis risk, while homozygous p.Q289X mutation is associated with higher dermatophytosis risk.
• Significant differences in CARD9 mutation spectrum and geographical distribution were observed between African and Asian patient populations, with Asian patients showing greater diversity.

Conclusions:

• The genetic landscape of CARD9 deficiency is diverse, with 32 identified mutations contributing to varied fungal infection susceptibilities.
• Specific CARD9 mutations exhibit geographical clustering and are associated with distinct fungal infection profiles.
• Understanding these genotype-phenotype and genotype-geotype correlations is crucial for managing fungal infections in CARD9-deficient individuals.