Congenital Hepatic Fibrosis in a Purebred Spanish Horse Foal: Pathology and Genetic Studies on PKHD1 Gene Mutations.
Authors: Molín Jéssica, Asín Javier, Vitoria Arantzazu, Sanz Arianne, Gimeno Marina, Romero Antonio, Sánchez Javier, Pinczowski Pedro, Vázquez Francisco J, Rodellar Clementina, Luján Lluís
Journal: Veterinary pathology
Summary
Congenital hepatic fibrosis (CHF) is a progressive and fatal liver condition documented in certain horse breeds, with previous research identifying PKHD1 gene mutations as causative in Swiss Franches-Montagnes horses. This case study examined a 1-month-old Purebred Spanish Horse foal that died from hepatic failure, conducting pathological analysis and comprehensive genetic sequencing to determine whether known PKHD1 mutations could explain the disease presentation in this breed. The affected foal carried the two previously documented SNPs associated with CHF in Swiss horses, but crucially also harboured two novel mutations—being homozygous for one and heterozygous for the other—suggesting a more complex genetic basis than currently understood. Screening of 35 healthy Purebred Spanish horses revealed that the known Swiss-associated SNPs occurred at 3-5 fold higher frequencies in this population, yet clinical CHF is not epidemic, indicating these variants alone do not fully account for disease manifestation in Spanish horses. Breeders and veterinarians working with Purebred Spanish horses should recognise that CHF may involve additional PKHD1 mutations beyond those characterised in other breeds, and that genetic testing protocols may require expansion to identify at-risk animals reliably.
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Practical Takeaways
- •Congenital hepatic fibrosis is a lethal condition in foals that should be considered in differential diagnosis of neonatal hepatic failure, particularly in Purebred Spanish horses
- •Genetic testing for PKHD1 mutations may be warranted in PSH breeding programs, though current SFM-identified mutations may not fully explain disease in this breed
- •Breeders of Purebred Spanish horses should be aware of potential breed-specific PKHD1 mutations and consider genetic counseling when planning matings
Key Findings
- •A 1-month-old Purebred Spanish Horse foal with congenital hepatic fibrosis was found to be heterozygous for 2 previously described PKHD1 SNPs and homozygous/heterozygous for 2 novel mutations
- •PKHD1 SNP g.49,630,834G>A showed 3-fold higher genotypic frequency in healthy PSH population (n=35) compared to Swiss Franches-Montagnes horses
- •PKHD1 SNP g.49,597,760A>T showed 5-fold higher genotypic frequency in healthy PSH population compared to Swiss Franches-Montagnes horses
- •SNPs identified in CHF-affected SFM horses may not fully explain CHF presentation in Purebred Spanish horses, suggesting additional PKHD1 mutations play a role