Hereditary and Acquired Immunodeficiencies

Giger, Urs; Reagan, Krystle L.

doi:10.1016/b978-0-323-50934-3.00130-0

Cited by 1 publication

(1 citation statement)

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“…Ensembl Variant Effect Predictor (VEP; RRID SCR_007931, v98) was used to annotate variants [ 20 ], and variants were further filtered for those predicted to have moderate or high impact on the protein (e.g., splice site, nonsense, frameshift, or missense). Based on the suspected autosomal recessive inheritance of PCP susceptibility in the CKCS breed [ 21 ], variants present in a homozygous state in D1 were prioritized. These variants were screened against an internal database of canine whole genome sequencing variant calls for 580 dogs of 57 breeds, including 21 CKCS dogs, to identify private and rare variants (allele frequency <0.005) [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia

Coffey,

Ma,

Cissé

et al. 2024

JoF

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Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

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Section: Methodsmentioning

confidence: 99%