An autosomal recessive nonsense variant in the EGFR gene induces perinatal lethality in “Blonde d'Aquitaine” calves

BACKGROUND: Six cases of perinatal lethality associated with phenotypes consistent across cases, short and brush-haired appearance, alopecia and erythematous areas on the limbs and facial protuberances, excess skin all-over the body, have recently occurred in the "Blonde d'Aquitaine" cattle breed in South-Western France, suggesting the emergence of a recessive genetic anomaly. RESULTS: Genetic analysis identified a nonsense variant in the epidermal growth factor receptor (EGFR) gene, XP_002696936:p.Trp898Ter, as likely responsible for this anomaly and a bull born in 1967 as one ancestor that contributed to the spread of this allele in the breed. Functional studies on affected calves and cross-species comparisons of the phenotypes associated with such a variant were consistent with the results of the genetic study. CONCLUSION: A recessive nonsense EGFR variant was identified as being responsible for perinatal lethality in the "Blonde d'Aquitaine" cattle breed. It enabled the introduction of a screening test for this allele, which should lead to the progressive eradication of this genetic flaw.