A Missense Variant in the Bardet-Biedl Syndrome 2 Gene (BBS2) Leads to a Novel Syndromic Retinal Degeneration in the Shetland Sheepdog

Genes

卷:12

Maria Kaukonen¹  Inka Pettinen¹  Hannes Lohi¹  David Sargan²  Frode Lingaas³  Cathryn S. Mellersh⁴  Rebekkah J. Hitti-Malin⁴  Louise M. Burmeister⁴ 

[1] Department of Veterinary Biosciences, Department of Medical and Clinical Genetics, University of Helsinki and Folkhälsan Research Center, 00014 Helsinki, Finland;

[2] Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK;

[3] Faculty of Veterinary Medicine and Biosciences, Department of Medical Genetics, Norwegian University of Life Sciences, P.O. Box 369 Sentrum, N-0102 Oslo, Norway;

[4] Kennel Club Genetics Centre, Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU, UK;

关键词: canine;    PRA;    retinal degeneration;    BBS;    BBS2;    syndromic;   

DOI  :  10.3390/genes12111771

来源: DOAJ

【 摘 要 】

Canine progressive retinal atrophy (PRA) describes a group of hereditary diseases characterized 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.

【 授权许可】

Unknown