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Background  Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine  LRP4  gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds.    Results  We confirmed the previously described  LRP4  exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new  LRP4  non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families.    Conclusion  We confirmed a significant role of  LRP4  mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the  LRP4  gene represent independent mutations affecting different conserved protein domains. However, the four newly described  LRP4  mutations do still not explain all analyzed cases of syndactyly.

Congenital syndactyly in cattle: four novel mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4)