05a1f0ec-2dc9-479f-94d4-7c618c8bbd04
A missense variant in the Bardet-Biedl Syndrome 2 gene (BBS2) leads to a novel syndromic retinal degeneration in the Shetland Sheepdog.
Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized by photoreceptor cell death in the retina. Disease progression, age of onset and etiology of PRA are variable, but vision loss is inevitable. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breeds, with many still genetically unsolved. This study sought to elucidate the causal variant for a distinct form of PRA in the Shetland Sheepdog using a whole-genome sequencing approach. Filtering variants from a single PRA-affected Shetland Sheepdog genome, compared to 176 genomes of other breeds, identified a single nucleotide variant in exon 11 of the Bardet-Biedl Syndrome-2 gene (BBS2) (c.1222G>C; p.A408P; CanFam3.1 assembly). Human BBS2 mutations cause Bardet-Biedl syndrome: a syndrome characterized by retinal degeneration accompanied by secondary features including obesity, dental, renal, and craniofacial defects. Genotyping 1,386 canids of 155 dog breeds, 15 cross breeds and eight wolves indicated the c.1222G>C variant was only present in Shetland Sheepdogs. Out of 505 Shetland Sheepdogs, seven were homozygous for the variant. Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, clinical signs exhibited include an upturned nose, abnormal coat, dental defects, obesity and renal defects, supporting the discovery of a novel syndromic PRA in the breed. To date, this is the third report of a Bardet-Biedl syndrome gene associated with canine PRA. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.
Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized by photoreceptor cell death in the retina. Disease progression, age of onset and etiology of PRA are variable, but vision loss is inevitable. Despite the identification of multiple PRA-causing variants, extensive heterogeneity of PRA is observed across and within dog breeds, with many still genetically unsolved. This study sought to elucidate the causal variant for a distinct form of PRA in the Shetland Sheepdog using a whole-genome sequencing approach. Filtering variants from a single PRA-affected Shetland Sheepdog genome, compared to 176 genomes of other breeds, identified a single nucleotide variant in exon 11 of the Bardet-Biedl Syndrome-2 gene (BBS2) (c.1222G>C; p.A408P; CanFam3.1 assembly). Human BBS2 mutations cause Bardet-Biedl syndrome: a syndrome characterized by retinal degeneration accompanied by secondary features including obesity, dental, renal, and craniofacial defects. Genotyping 1,386 canids of 155 dog breeds, 15 cross breeds and eight wolves indicated the c.1222G>C variant was only present in Shetland Sheepdogs. Out of 505 Shetland Sheepdogs, seven were homozygous for the variant. Clinical history and photographs for three homozygotes indicated the presence of a novel phenotype. In addition to PRA, clinical signs exhibited include an upturned nose, abnormal coat, dental defects, obesity and renal defects, supporting the discovery of a novel syndromic PRA in the breed. To date, this is the third report of a Bardet-Biedl syndrome gene associated with canine PRA. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.