In other species: Mexican tetra , corn snake

Possibly relevant human trait(s) and/or gene(s) (MIM number): 203200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2017

Cross-species summary: Tyrosinase-positive oculocutaneous albinism (OCA, type II) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in skin, hair, and eyes.

Mapping: Caduff et al. (2017) performed linkage analysis and autozygosity mapping in a family of German Spitzes consisting of both non-affected parents, three affected puppies and three non-affected puppies. Only one ~15 Mb genome segment, Chr3:28,747,944 - 43,731,542 (CanFam 3.1) showed both linkage and homozygosity with shared alleles across the cases.

Molecular basis: The OCA2 gene is located in the critical interval on chromosome 3. Whole genome sequencing of one of the affected dogs revealed a splice site variant in the OCA2 gene that co-segregated with the phenotype in the German Spitz family. The variant did not occur in 181 normally pigmented dogs from various breeds. As OCA2 loss of function variants have been shown to cause oculocutaneous albinism in many other species, the OCA2 variant represents a compelling candidate causative variant. The variant is not easy to describe as the study by Caduff et al. (2017) also unveiled an assembly error concerning the OCA2 gene in the CanFam 3.1 genome reference assembly. The variant affects the conserved GT dinucleotide at the 5'-splice site of an early intron. It can be described as Chr3:31,715,704A>C (CanFam3.1) or OCA2:LT844587.1:c.-45+2T>G.

Clinical features: The three affected German Spitz puppies reported in Caduff et al. (2017) showed a light brown (hazel) coat colour and blue eyes. Pigmentation of the coat and eyes became slightly darker with age. The owner reported that the affected puppies used to squint in bright sunlight (photophobia) and had difficulties to perceive hand signals in bright sunlight. Photophobia and mild to moderate visual deficits are also common in human patients with oculocutaneous albinism type II.

Breed: German Spitz.

Associated gene: