Congenital myasthenia in Brahman calves caused by homozygosity for a CHRNE truncating mutation.

To elucidate the genetic defect in four previously reported related Brahman calves with severe myasthenic weakness, we determined the genomic structure of the gene encoding the bovine epsilon-subunit (bovCHRNE) of the acetylcholine receptor (AChR). Amplification of DNA isolated from paraplast-embedded tissue samples from one of the myasthenic calves and subsequent sequencing of all bovCHRNE exons revealed a homozygous 20-bp deletion within exon 5 (470del20). The deletion causes a frame shift followed by a premature stop codon in the predicted bovCHRNE protein. Thus, the 470del20 mutation reported here leads to a non-functional allele, explaining the impairment of neuromuscular transmission observed in the affected Brahman calves. With a survival time limited to only several months, the effect on neuromuscular transmission was more pronounced in the calves than that observed in humans homozygous for truncating CHRNE mutations. This may be due to a different capacity to express the fetal-type AChR after birth.