Clinical and molecular genetic description of a Marfan-like syndrome in a Golden Retriever puppy.

backgroundMarfan syndrome (MFS) is a genetic fibrillin disorder causing cardiac, ocular, and musculoskeletal pathology; it is not well reported on in dogs, with minimal descriptions of antemortem diagnosis. HYPOTHESIS/

objectivesUse whole-genome sequencing (WGS) to diagnose a dog with suspected MFS to guide prognostication and potential treatment. ANIMALS: A client-owned, 10-month-old Golden Retriever presented with signs of possible connective tissue disorder. Blood and DNA samples from a non-affected German Shepherd-Beagle mix and 160 unrelated Golden Retrievers were used as controls.

methodsPhysical examination, blood collection, and radiography were performed on the dog while at the hospital. Whole-genome sequencing was performed on DNA from the affected dog. Genetic analysis focused on single-nucleotide variants, small insertion-deletions, and structural variants to detect potential disease-causing genetic variants in the genome, prioritizing candidate genes. Polymerase chain reaction amplification and Sanger sequencing of a suspected region were carried out to confirm presence of the candidate pathogenic variant.

resultsThe dog was presented for cardiology consultation and had clinical signs of cardiac enlargement, pneumothorax, and joint hypermobility. After genetic analysis, a 3618 base pair deletion encompassing exon 24 of the FBN1 gene on 1 allele was detected (NC_049251.1:g.14998228_15001846del), likely causing an in-frame deletion in the coding sequence. CONCLUSIONS AND CLINICAL IMPORTANCE: Physical and complementary examination findings are suggestive of MFS and associated with a causal deletion variant.