Inherited CARD9 Deficiency Due to a Founder Effect in East Asia

• DOI: 10.1007/s10875-024-01724-7
• Publication Date: 2024-05-17T04:01:50Z
• Authors: Dan Tomomasa; Beom Hee Lee; Yuki Hirata; Yuzaburo Inoue; Hidetaka Majima; Yusuke Imanaka; Takaki Asano; Takashi Katakami; Jina Lee; Atsushi Hijikata; Wittawin Worakitc...; Xi Yang; Xiaowen Wang; Akira Watanabe; Katsuhiko Kamei; Yasufumi Kageyama; Go Hun Seo; Akihiro Fujimoto; Jean-Laurent Casa...; Anne Puel; Tomohiro Morio; Satoshi Okada; Hirokazu Kanegane
• Keywords: Male; Adult; Asia, Eastern; Candidiasis, Chronic Mucocutaneous; Founder Effect; Pedigree; CARD Signaling Adaptor Proteins; Haplotypes; Asian People; Mutation; Candida albicans; Humans; Female; Alleles

Autosomal recessive CARD9 deficiency can underly deep and superficial fungal diseases. We identified two Japanese patients, suffering from superficial and invasive Candida albicans diseases, carrying biallelic variants of CARD9. Both patients, in addition to another Japanese and two Korean patients who were previously reported, carried the c.820dup CARD9 variant, either in the homozygous (two patients) or heterozygous (three patients) state. The other CARD9 alleles were c.104G > A, c.1534C > T and c.1558del. The c.820dup CARD9 variant has thus been reported, in the homozygous or heterozygous state, in patients originating from China, Japan, or South Korea. The Japanese, Korean, and Chinese patients share a 10 Kb haplotype encompassing the c.820dup CARD9 variant. This variant thus originates from a common ancestor, estimated to have lived less than 4,000 years ago. While phaeohyphomycosis caused by Phialophora spp. was common in the Chinese patients, none of the five patients in our study displayed Phialophora spp.-induced disease. This difference between Chinese and our patients probably results from environmental factors. (161/250).