In other species: domestic cat , ass , Arabian camel , cattle , goat

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 172800 (trait) , 164920 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism"), not by failure in the biochemical reactions required for pigment synthesis.

History: The first occurrence of this particular trait was due to a mutation in a German Shepherd sire

Inheritance: The white-spotting allele in this family of German Shepherds is autosomal dominant with respect to coat colour and recessive lethal with respect to viability (Wong et al., 2013).

Mapping: A genome scan of 95 German Shepherd dogs with 143 microsatellites enabled Wong et al. (2013) to linkage map the white-spotting locus in this pedigree to a single region on chromosome CFA13 which contains the KIT gene.

Molecular basis: Sequencing of exons of the KIT gene by Wong et al. (2013) revealed "a 1-bp insertion of an adenine 70 bases downstream of the beginning of exon 2.", i.e. a frameshift mutation. The authors also reported that "Subsequent genotyping showed that the insertion was perfectly associated with the phenotype (64 spotted dogs and 31 normal littermates; P < 0.001). The mutation was a de novo event – observed in the proband but absent in both parents. . . . The insertion occurred in codon 47 (of 976 codons) and was expected to produce a frameshift with the first downstream premature stop at codon 57. Consequently, the allele was predicted to produce a severely truncated product (55/974 amino acid residues . . .). Given previous characterizations of c-Kit, the mutant protein was likely to be non-functional, implying that the dominant white spotting resulted from haploinsufficiency."

Gerding et al. (2013) reported a de novo KIT mutation (a 3-bp deletion [c.1960_1962delCTC (p.Leu654del)] in exon 13 of the KIT gene . . . [which] shortens the tyrosine kinase domain 1 of the KIT protein by one amino acid and hence affects the receptor's functionality with high probability) as the cause of "a spotted Weimaraner with exceptional coat colour patterning exhibiting a white blaze on the head extending to the back, white ventral abdomen, white tips on the extremities and overall lightened colour of the ‘greyish’ pigmented areas."

Breed: German Shepherd Dog.

Associated gene: