A missense variant in the Bardet-Biedl syndrome 2 gene (BBS2) leads to a novel syndromic retinal degeneration in the shetland sheepdog

Rebekkah J. Hitti-Malin, Louise M. Burmeister*, Frode Lingaas, Maria Kaukonen, Inka Pettinen, Hannes Lohi, David Sargan, Cathryn S. Mellersh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases char-acterized by photoreceptor cell death in the retina, leading to visual impairment. 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.Ala408Pro). Genotyping 1386 canids of 155 dog breeds, 15 cross breeds and 8 wolves indicated the c.1222G>C variant was only segregated within 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, additional clinical features in homozygous dogs support the discovery of a novel syndromic PRA in the breed. The development and utilization of a diagnostic DNA test aim to prevent the mutation from becoming more prevalent in the breed.

Original languageEnglish
Article number1771
JournalGenes
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2021
Externally publishedYes

Keywords

  • BBS
  • BBS2
  • Canine
  • PRA
  • Retinal degeneration
  • Syndromic

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