title: A deletion in FOXN1 is associated with a syndrome characterized by congenital hypotrichosis and short life expectancy in Birman cats.
abstract: An autosomal recessive syndrome characterized by congenital hypotrichosis and short life expectancy has been described in the Birman cat breed (Felis silvestris catus). We hypothesized that a FOXN1 (forkhead box N1) loss-of-function allele, associated with the nude phenotype in humans, mice and rats, may account for the syndrome observed in Birman cats. To the best of our knowledge, spontaneous mutations in FOXN1 have never been described in non-human, non-rodent mammalian species. We identified a recessive c.1030_1033delCTGT deletion in FOXN1 in Birman cats. This 4-bp deletion was associated with the syndrome when present in two copies. Percentage of healthy carriers in our French panel of genotyped Birman cats was estimated to be 3.2%. The deletion led to a frameshift and a premature stop codon at position 547 in the protein. In silico, the truncated FOXN1 protein was predicted to lack the activation domain and critical parts of the forkhead DNA binding domain, both involved in the interaction between FOXN1 and its targets, a mandatory step to promote normal hair and thymic epithelial development. Our results enlarge the panel of recessive FOXN1 loss-of-function alleles described in mammals. A DNA test is available; it will help owners avoid matings at risk and should prevent the dissemination of this morbid mutation in domestic felines.
authors.affiliation: U955 IMRB, INSERM, Équipe 10, Créteil, France; BNMS-Génétique Médicale Comparée des Affections Neuromusculaires, École nationale vétérinaire d'Alfort, Maisons-Alfort, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Abitbol
authors.affiliation: U955 IMRB, INSERM, Équipe 10, Créteil, France; BNMS-Génétique Médicale Comparée des Affections Neuromusculaires, École nationale vétérinaire d'Alfort, Maisons-Alfort, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bossé
authors.affiliation: Antagene, La Tour de Salvagny, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thomas
authors.affiliation: U955 IMRB, INSERM, Équipe 10, Créteil, France; BNMS-Génétique Médicale Comparée des Affections Neuromusculaires, École nationale vétérinaire d'Alfort, Maisons-Alfort, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Tiret
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002415:Cats / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics*; D017353:Gene Deletion; D005787:Gene Frequency; D007039:Hypotrichosis / Q000151:congenital / Q000662:veterinary*; D008017:Life Expectancy; D008969:Molecular Sequence Data
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein