biostudies-literatureCoffey ELNCATS NIH HHSNIH Special Emphasis Research Career AwardNIH Office of the Director Special Emphasis Research Career AwardNIH HHSthe Intramural Research Program of the National Institutes of Health (NIH) Clinical Center, NIH, Bethesda, MarylandDivision of Comparative Medicine, Office of Research Infrastructure ProgramsNIH National Center for Advancing Translational Sciences198https://www.ebi.ac.uk/biostudies/studies/S-EPMC10970956biostudies-literatureUnknown10(3)Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to <i>Pneumocystis</i> and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for <i>Pneumocystis</i> pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a <i>CARMIL2</i> nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory <i>Bordetella</i> pneumonia (n = 1). <i>CARMIL2</i> encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious <i>CARMIL2</i> variants have recently been reported in human patients with PCP and other recurrent Journal of fungi (Basel, Switzerland)A Novel <i>CARMIL2</i> Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with <i>Pneumocystis</i> and <i>Bordetella</i> Pneumonia.PMC10970956UL1 TR0024941 K01 OD027058KL2 TR002492K01 OD027058K01 OD019912K01OD027058UL1TR002494K01OD019912Granick MNMinor KMMa LKovacs JACisse OHCullen JNSukura AFriedenberg SGWeissenbacher-Lang CNadeau JCGraham AMJacobs CMFurrow EBranson KCCoffey ELDanesi PBranson NKBlasi BfalseA Novel <i>CARMIL2</i> Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with <i>Pneumocystis</i> and <i>Bordetella</i> Pneumonia.Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to <i>Pneumocystis</i> and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for <i>Pneumocystis</i> pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a <i>CARMIL2</i> nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory <i>Bordetella</i> pneumonia (n = 1). <i>CARMIL2</i> encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious <i>CARMIL2</i> variants have recently been reported in human patients with PCP and other recurrent 2024-01-01T00:00:00Z2024 Mar2026-07-09T10:48:08.549Z2025-05-31T23:11:56.305ZS-EPMC109709563853520710.3390/jof10030198