The developmental pathways involved in horn development are complex and still 
poorly understood. Here we report the description of a new dominant inherited 
syndrome in the bovine Charolais breed that we have named type 2 scurs. Clinical 
examination revealed that, despite a strong phenotypic variability, all affected 
individuals show both horn abnormalities similar to classical scurs phenotype 
and skull interfrontal suture synostosis. Based on a genome-wide linkage 
analysis using Illumina BovineSNP50 BeadChip genotyping data from 57 half-sib 
and full-sib progeny, this locus was mapped to a 1.7 Mb interval on bovine 
chromosome 4. Within this region, the TWIST1 gene encoding a transcription 
factor was considered as a strong candidate gene since its haploinsufficiency is 
responsible for the human Saethre-Chotzen syndrome, characterized by skull 
coronal suture synostosis. Sequencing of the TWIST1 gene identified a 
c.148_157dup (p.A56RfsX87) frame-shift mutation predicted to completely 
inactivate this gene. Genotyping 17 scurred and 20 horned founders of our 
pedigree as well as 48 unrelated horned controls revealed a perfect association 
between this mutation and the type 2 scurs phenotype. Subsequent genotyping of 
32 individuals born from heterozygous parents showed that homozygous mutated 
progeny are completely absent, which is consistent with the embryonic lethality 
reported in Drosophila and mouse suffering from TWIST1 complete insufficiency. 
Finally, data from previous studies on model species and a fine description of 
type 2 scurs symptoms allowed us to propose different mechanisms to explain the 
features of this syndrome. In conclusion, this first report on the 
identification of a potential causal mutation affecting horn development in 
cattle offers a unique opportunity to better understand horn ontogenesis.