Recessive SLC25A12 mutation linked to brain defect in Limousin calves in Great Britain

A recessively inherited variant in the SLC25A12 gene has been linked to porencephaly in Limousin cattle in Great Britain, according to a study in Genetics Selection Evolution. Thirty-four affected calves were reported, and 16 of them underwent clinicopathological investigation. In three cases, whole-genome mapping and sequencing identified a homozygous missense variant on chromosome 2 biomedcentral.comGenetics Selection Evolutionbiomedcentral.comOpen source ↗.

Phenotype of affected calves

The affected calves were blind and stuporous from birth and could not suckle without assistance. Brain examination showed a bilateral symmetrical cavity in the cerebral cortex, which is porencephaly.

Some calves also showed ongoing degeneration of the cerebellar cortex, described as cerebellar abiotrophy. It included focal spindle-shaped swellings on the proximal axons of Purkinje cells, known as "torpedoes", in the inner granular layer, and intra-myelinic phagocytes in the white matter of the cerebellar folia.

Porencephaly in cattle is often virus-induced. Here, PCR testing excluded common teratogenic viruses, and pedigree analysis pointed to monogenic recessive inheritance biomedcentral.comGenetics Selection Evolutionbiomedcentral.comOpen source ↗. According to bioengineer.org, 24 calves with genealogical records traced back within six generations to a common sire, an artificial insemination bull named Sy, born in France in 2001 and exported to the United Kingdom.

Genetic findings

Mapping identified a unique homozygous region of 1.2 Mb on chromosome 2. It contains a private homozygous missense variant in SLC25A12 (NM_001101194.2: c.1742G > A; NP_001094664.1: p.(Arg581Gln)) in three cases. The variant was absent in more than 5,000 control genomes.

The gene encodes a calcium-binding mitochondrial carrier protein and is a known candidate for neurogenetic disorders. Genotyping confirmed recessive inheritance in a random study cohort of British Limousins. The allele frequency was close to 0% in the studied French and Swiss Limousin populations.

The authors describe this as the first SLC25A12-related neurodevelopmental disorder in a domestic animal species and assume that the variant impairs the normal function of the protein. They propose it as a new spontaneous large-animal model for similar human conditions biomedcentral.comGenetics Selection Evolutionbiomedcentral.comOpen source ↗.

The authors recommend considering the allele in breeding programs to prevent risk matings. Because several neurogenetic disorders share their morphology with virus-induced malformations, they advise virus testing for aborted, stillborn or live-born calves with porencephaly alongside a possible genetic cause.