Abstract
Dyserythropoietic anemia and myopathy syndrome (DAMS) with neonatal losses was recently characterized as an autosomal recessive disorder caused by an EHBP1L1 frameshift variant in English Springer Spaniels (ESSPs). The frequency and dissemination of the mutation remained unknown. The EHBP1L1 protein is essential for muscle function, and the Rab8/10-EHBP1L1-Bin1-dynamin axis participates in nuclear polarization during the enucleation of erythroblasts. Lack of EHBP1L1 function decreases enucleation, leading to increased numbers of nucleated erythrocytes, which are characteristic of DAMS. A genotyping survey for the EHBP1L1 variant was conducted based upon submitted samples of ESSPs from Europe. DNA was extracted, and a real-time PCR assay, with allele-specific TaqMan probes for EHBP1L1 wild-type and frameshift deletion, was applied. Between September 2022 and August 2024, 803 samples were received from 18 European countries. The EHBP1L1 mutant allele frequency was 9.7%, including 4 homozygous dogs and 148 heterozygotes. The mutant EHBP1L1 allele was found in 13 countries. A total of 6 homozygous and 73 heterozygous ESSPs reported on an open database could be tracked to an original common ancestor. Although the survey is biased, it indicates that the mutant EHBP1L1 variant is disseminated in the breed and across Europe. The genotyping of ESSPs is recommended to diagnose DAMS and guide breeders.