Hypertriglyceridemia (HTG) may be inherited and caused by variants in genes encoding enzymes oflipid 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 termedthis phenotype hypertriglyceridemia-induced pancreatitis (HIP). The affected foals were distantlyrelated and inbred to a prominent stallion suggesting autosomal recessive inheritance. Whole genomesequencing of an affected foal identified a homozygous loss of function variant in LMF1 encoding lipasematuration factor 1. The variant, XM_023616679.1:c.369_373delinsTCT, leads to an early frameshiftand is predicted to alter or truncate 78% of the LMF1 coding sequence. We genotyped the variant in acohort of 2122 FM horses and identified 11 homozygous mutant animals including all eight foals thathad initially been identified based on their clinical presentation. The three additional homozygousmutant animals had a comparable phenotype and were inbred to the same stallion. We concluded thatall 11 had been affected by the same disease. Thus, we found perfect genotype-phenotype associationin the tested cohort. The carrier frequency in the 2111 unaffected FM horses was 15.0%. Our findingsenable genetic testing to prevent the unintentional breeding of further HIP-affected foals.
