title: A mutation in NFkappaB interacting protein 1 causes cardiomyopathy and woolly haircoat syndrome of Poll Hereford cattle.
abstract: Cardiomyopathy and woolly haircoat syndrome (CWH) of Poll Hereford cattle is a lethal, autosomal recessive disorder. Cardiac and haircoat changes are congenital, neonatal ocular keratitis develops in some cases and death usually occurs within the first 12 weeks of life. We undertook a homozygosity mapping approach to identify the chromosomal location of the causative gene. Seven candidate genes were examined for homozygosity in affected animals: desmoplakin and junction plakoglobin (both previously implicated in human cardiocutaneous syndromes), desmocollin 2, desmoglein 2, plakophilin 2, nuclear factor kappa B (NFKB1) and NFkappaB interacting protein 1 (PPP1R13L, also known as NKIP1). Homozygosity in 13 affected animals was observed at the PPP1R13L locus, located on bovine chromosome 18. Subsequent sequence analysis revealed a 7-bp duplication (c.956_962dup7) in exon 6 of this 13-exon gene. This frameshift variant is predicted to result in the substitution of three amino acids and the introduction of a premature stop codon at position 325 of the protein product (p.Ser322GlnfsX4). PPP1R13L interacts with NFkappaB, a family of structurally related transcription factors that regulate genes controlling inflammation, immune responses and cell proliferation and survival. CWH represents a large-animal model for cardiocutaneous disorders caused by a mutation in the PPP1R13L gene. The identification of this bovine mutation also indicates that PPP1R13L and other genes affecting NFkappaB activity may be candidate genes in the study of human cardiovascular disease.
authors.affiliation: Medical Genetics, Clinical Developmental Sciences, St George's University of London, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Simpson
authors.forename: R W
authors.initials: RW
authors.lastname: Cook
authors.forename: P
authors.initials: P
authors.lastname: Solanki
authors.forename: M A
authors.initials: MA
authors.lastname: Patton
authors.forename: J A
authors.initials: JA
authors.lastname: Dennis
authors.forename: A H
authors.initials: AH
authors.lastname: Crosby
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000662:veterinary*; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics*; D006201:Hair Diseases / Q000235:genetics / Q000662:veterinary*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D013577:Syndrome
chemical_list: D047908:Intracellular Signaling Peptides and Proteins