title: A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs.
abstract: Autosomal recessive congenital ichthyosis in the American bulldog is characterized by generalized scaling and erythema with adherent scale on the glabrous skin. We had previously linked this disorder to NIPAL4, which encodes the protein ichthyin. Sequencing of NIPAL4 revealed a homozygous single base deletion (CanFam3.1 canine reference genome sequence NC_06586.3 g.52737379del), the 157th base (cytosine) in exon 6 of NIPAL4 as the most likely causative variant in affected dogs. This frameshift deletion results in a premature stop codon producing a truncated and defective NIPAL4 (ichthyin) protein of 248 amino acids instead of the wild-type length of 404. Obligate carriers were confirmed to be heterozygous for this variant, and 150 clinically non-affected dogs of other breeds were homozygous for the wild-type gene. Among 800 American bulldogs tested, 34% of clinically healthy dogs were discovered to be heterozygous for the defective allele. More importantly, the development of this canine model of autosomal recessive congenital ichthyosis will provide insight into the development of new treatments across species.
authors.affiliation: Section of Medical Genetics, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Margret L
authors.initials: ML
authors.lastname: Casal
authors.affiliation: Section of Medical Genetics, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mauldin
authors.affiliation: Section of Medical Genetics, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lin
authors.affiliation: Section of Medical Genetics, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Henthorn
mesh_terms: D000483:Alleles; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005808:Genes, Recessive; D007057:Ichthyosis / Q000235:genetics / Q000662:veterinary*; D009154:Mutation; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface