In other species: domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 612768 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Mapping: By conducting a GWAS on 84 Weimaraner dogs "(40 males and 44 females) of whom 14 were affecteds, 19 were known carriers, and 51 were unaffecteds", each genotyped with the Illumina CanineHD BeadChip (yielding 95,990 informative autosomal SNPs), Pemberton et al. (2014) mapped this disorder to a 5Mb region (57.3 to 62.3) on chromosome CFA15. Subsequent homozygosity mapping narrowed this to a 3.7Mb region (573. to 61.0).

Molecular basis: After sequencing the most obvious candidate gene in the candidate region (see Mapping section) and discovering no mutations, Pemberton et al. (2014) sequenced all 199 exons of the remaining 16 genes in that region, yielding 54 variants, only one of which had the potential to be deleterious. This variant turned out to be the causal mutation: "a deletion of a single A nucleotide within exon 9 of the gene encoding folliculin-interacting protein 2 (FNIP2). This mutation at nucleotide 880 of the coding sequence (c.880delA, XM_532705) causes a frameshift, and the amino acid sequence is altered beginning at codon 294, with a premature translation stop signal introduced at codon 296 . . . . A highly truncated protein of 295 amino acids compared with the wild-type protein of 1,106 amino acids is predicted to result from this p.Ile294fsX296 mutation"

Associated gene: