Novel LIPC-related recessive form of postural proprioceptive deficits in Brown Swiss cattle

Genetic neuromuscular disorders (NMDs) are characterized by progressive skeletal muscle degeneration and weakness. In Brown Swiss (BS) cattle, three recessive variants have been associated with NMDs. This study aimed to (1) describe the phenotype of BS cattle affected by a novel form of postural proprioceptive deficits, (2) identify a candidate genetic variant using whole-genome sequencing (WGS), and (3) estimate its prevalence in the Swiss BS population. A first BS heifer (case 1) showing ataxia underwent clinical and hematological examination, followed by WGS of the heifer and its sire. Variants were filtered and compared against 5577 controls. Candidate variants were evaluated in silico for predicted pathogenicity, genotyped in national breeding cohorts, and clinically assessed in additional homozygous animals. A rare homozygous missense variant in LIPC (chr10:51715800G>C; NM_001035410.1:c.924C>G; p.Phe308Leu; omia.variant:1842) was identified and in-silico predictions classified this variant as deleterious. Population-level genotyping of over 20.000 BS cattle revealed a variant allele frequency of 17% with significant deviation from the Hardy–Weinberg equilibrium (p-value=1.14 × 10⁻20), suggesting possible lethality in homozygotes. Case 1, as well as 11 additional LIPC-homozygous BS females (mean age 2.4 ± 0.2 years), exhibited consistent neurological signs, including postural deficits and subconscious proprioceptive ataxia. Biochemical profiles revealed hypercholesterolemia, hypertriglyceridemia, and decreased HDL cholesterol, suggesting dyslipidemia. Pedigree analysis identified a shared ancestor and inbreeding loops, supporting recessive inheritance. This study describes a novel autosomal recessive LIPC-related juvenile-onset NMD in BS cattle characterized by postural proprioceptive deficits with a tendency towards dyslipidemia. More research is needed to better understand the effects of the identified variant and prove that it is the cause.