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LMF1 frameshift deletion in Franches-Montagnes horses with hypertriglyceridemia-induced pancreatitis.
Abstract: Hypertriglyceridemia (HTG) may be inherited and caused by variants in genes encoding enzymes of lipid metabolism. This study was prompted by the observation of eight Franches-Montagnes (FM) foals showing elevated plasma triglyceride levels and episodes of fatal acute pancreatitis. We termed this phenotype hypertriglyceridemia-induced pancreatitis (HIP). The affected foals were distantly related and inbred to a prominent stallion suggesting autosomal recessive inheritance. Whole genome sequencing of an affected foal identified a homozygous loss of function variant in LMF1 encoding lipase maturation factor 1. The variant, XM_023616679.1:c.369_373delinsTCT, leads to an early frameshift and is predicted to alter or truncate 78% of the LMF1 coding sequence. We genotyped the variant in a cohort of 2122 FM horses and identified 11 homozygous mutant animals including all eight foals that had initially been identified based on their clinical presentation. The three additional homozygous mutant animals had a comparable phenotype and were inbred to the same stallion. We concluded that all 11 had been affected by the same disease. Thus, we found perfect genotype-phenotype association in the tested cohort. The carrier frequency in the 2111 unaffected FM horses was 15.0%. Our findings enable genetic testing to prevent the unintentional breeding of further HIP-affected foals.
© 2025. The Author(s).
Publication Date: 2025-08-06 PubMed ID: 40764662PubMed Central: PMC12326015DOI: 10.1038/s41598-025-13954-9Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research study investigates a particular type of horse known as Franches-Montagnes (FM) which suffer from a condition termed hypertriglyceridemia-induced pancreatitis (HIP). The condition, which triggers fatal acute pancreatitis due to elevated plasma triglyceride levels, was found to be linked to genetic mutations, specifically a loss-of-function variant in LMF1 gene which encodes lipase maturation factor 1. The study envisions to prevent the breeding of HIP-affected foals through genetic testing.
Research Purpose and Background
- The researchers embarked on this study after identifying eight Franches-Montagnes (FM) foals experiencing increased plasma triglyceride levels and episodes of deadly acute pancreatitis.
- In order to explore the origins of the disease, the researchers considered the possibility of genetic inheritance, as the affected foals were distantly related and inbred to a prominent stallion. This suggested an autosomal recessive inheritance pattern.
Genomic Examination and Discovery of a Genetic Variant
- A whole genome sequencing of an affected foal was done to pinpoint any possible genetic abnormalities. The sequencing revealed a homozygous loss-of-function variant in the LMF1 gene, which encodes lipase maturation factor 1.
- Additionally, the researchers found a variant, named XM_023616679.1:c.369_373delinsTCT, that led to an early frameshift predicted to alter or truncate 78% of the LMF1 coding sequence, potentially causing the hypertriglyceridemia-induced pancreatitis.
Disease Association and Genotyping
- The variant was genotyped in a cohort of 2122 FM horses, resulting in 11 horses being identified as homozygous mutant animals, confirming the genetic variant’s association with the disease.
- These included all eight foals initially identified due to their clinical condition, as well as three additional animals with a similar phenotype and a common ancestry to the same stallion.
Genotype-Phenotype Relationship and Carrier Frequency
- Based on the findings, the researchers were able to draw a perfect genotype-phenotype association in the sample cohort.
- The study revealed a 15% carrier frequency amongst 2111 unaffected FM horses.
Conclusions and Implications
- The research affirms that the disease found in the FM horses is genetic in nature due to the connection with the LMF1 variant discovered.
- The findings support enabling genetic testing as a preventive measure to avoid continued breeding of HIP-affected foals thereby preventing the propagation of this fatal genetic condition.
Cite This Article
APA
Drögemüller M, Fouché N, Wyler M, Gurtner C, Meister SL, Neuditschko M, Jagannathan V, Gerber V, Leeb T.
(2025).
LMF1 frameshift deletion in Franches-Montagnes horses with hypertriglyceridemia-induced pancreatitis.
Sci Rep, 15(1), 28667.
https://doi.org/10.1038/s41598-025-13954-9 Publication
Researcher Affiliations
- Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Animal GenoPhenomics, Agroscope, Route de la Tioleyre 4, 1725, Posieux, Switzerland.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Swiss Institute of Equine Medicine, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland.
- Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001, Bern, Switzerland. tosso.leeb@unibe.ch.
MeSH Terms
- Animals
- Horses
- Hypertriglyceridemia / genetics
- Hypertriglyceridemia / veterinary
- Hypertriglyceridemia / complications
- Pancreatitis / genetics
- Pancreatitis / veterinary
- Pancreatitis / etiology
- Horse Diseases / genetics
- Horse Diseases / pathology
- Frameshift Mutation
- Male
- Homozygote
- Phenotype
- Genetic Association Studies
- Female
Grant Funding
- 627003244 / Bundesamt fu00fcr Landwirtschaft
- 627003244 / Bundesamt fu00fcr Landwirtschaft
- 627003244 / Bundesamt fu00fcr Landwirtschaft
- 627003244 / Bundesamt fu00fcr Landwirtschaft
Conflict of Interest Statement
Declarations. Competing interests: The authors declare no competing interests.
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