Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity

摘要

Genetic analysis, mutation characterization, clinical images, and pathological and immunophenotypic findings in the patients. a Pedigree of the CARD10-deficient family. The pedigree shows five generations of the family. Roman numerals refer to generations. Circles refer to female subjects. Squares refer to male subjects. Solid symbols refer to affected subjects. Crossed-out symbols refer to deceased subjects. The arrow indicates the proband. b High-resolution computed tomography of the proband at the age of 42 revealed bronchiectasis with infection, lung abscess, and pulmonary bulla. c H&E micrograph (×100 magnification) of the gastrointestinal mucosal biopsy sample of the proband’s sister at the age of 42 showing local proliferative gastritis and colitis. d Exon structure of the CARD10 gene. Domain structure of the CARD10 protein; aa amino acid number. e Sequence alignment of mammalian CARD10 proteins. R420, marked by the red box, is located in a highly conserved amino acid region (from UniProt). f The CARD10 protein tertiary structure was predicted by Swiss-model software based on the crystal structure of a coiled-coil segment of Pyrococcus yayanosii Smc (5xg2.1.pdb). The amino acid substitution from arginine to cysteine at position 420 likely affects intramolecular hydrogen bond formation, which is predicted to affect the hydrophobicity and stability of the alpha helix. g Sanger sequencing analysis of the CARD10 gene in the patients, their family members, and the controls. h Analysis of CD14 and CD16 expression on monocytes, CD45RA and CCR7 expression on CD3+CD4+ cells, CD1C and CD16 expression on DCs and CD1C and Clec9A expression on CD11c+DCs