Novel bi‐allelic splice mutations in CARD 9 causing adult‐onset Candida endophthalmitis

• Published in: Mycoses 2018-01, Vol.61 (1), p.61-65
• Main Authors: Gavino, Christina, Mellinghoff, Sibylle, Cornely, Oliver A., Landekic, Marija, Le, Catherine, Langelier, Melanie, Golizeh, Makan, Proske, Susanna, Vinh, Donald C.
• Format: Article
• Language: English
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/myc.12701

CARD 9 deficiency ( CANDF 2; OMIM # 212050) is an autosomal‐recessive monogenic inborn error of immunity conferring susceptibility to invasive fungal diseases, including the very distinct syndrome of spontaneous central nervous system candidiasis, in which opportunistic yeast of the genus Candida infect the central nervous system (either brain parenchyma and/or meninges) in the absence of trauma, chemotherapy or underlying systemic disease. We present a patient with spontaneous endophthalmitis of the right eye due to Candida albicans ; further investigations revealed concomitant cerebral abscess. She had a history of left endophthalmitis due to the dematiaceous mould, Aureobasidium pullulans , 15 years earlier. Targeted sequencing of the CARD 9 gene revealed 2 novel variants (c.184G>A and c.288C>T). Analysis in silico predicted each variant altered splicing, which was confirmed by sequencing of cDNA from proband and carrier offsprings: c.184G>A results in a 4‐base pair frameshift deletion with loss of allelic expression; c.288C>T results in an in‐frame 36‐bp pair deletion with detectable protein. CARD 9 deficiency can present with a phenotype of spontaneous candidal endophthalmitis. We report 2 novel mutations in CARD 9 , both affecting splicing, expanding the range of morbid variants causing CARD 9 deficiency, emphasising the importance of both genomic and cDNA sequencing for this condition.