Objective:

Investigate the genetic basis and molecular effects of Marfan syndrome in two affected domestic cats.

Approach:

• Clinical assessment: Researchers described two male littermates, Gary and Shaggy, with displaced eye lenses, unusually long limbs, and severe aortic enlargement.
• Genetic and RNA analysis: The team used whole-genome sequencing to identify a shared FBN1 variant and long-read RNA sequencing to assess its effects on gene transcripts.

Key Findings:

• Both cats carried the same rare FBN1 variant, which was absent from genomic data for more than 1,000 other cats.
• About 73% of FBN1 transcripts in the affected cat lacked exon 22; the remaining transcripts retained it.
• The authors proposed that retained transcripts may allow some normal fibrillin-1 production and help explain the cats’ survival into adulthood despite carrying two variant copies.

Interpretation:

The study reports the first documented feline case of Marfan syndrome and shows how RNA analysis can reveal effects of a genetic variant that DNA sequencing alone may not establish.

Limitations:

• The findings are based on two related cats.
• Fibrillin-1 protein production was not directly analyzed.

Conclusion:

The authors describe combining clinical findings, tissue pathology, genomic sequencing, and RNA analysis to investigate the consequences of rare genetic variants.

Sources:

• Article context; study published in Scientific Reports