Scurs, type 2, (possible abdominal hernia), TWIST1-related

Gene: TWIST1

Transmission: Autosomal, dominant (variable penetration)

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by a de novo mutation.

Mutation: Duplication, TWIST1 gene; c.148_157 dup, p.(Ala56Arg frameshift STOP 87), chromosome 4.

Breed: Charolais

Medical system: Skeletal, muscular.

Age of onset of symptoms: With birth but may not be noticed until later in life.

Scur is a defect in horn development seen in certain breeds of cattle that presents as an intermediate phenotype between normal horned and hornless (polled) phenotypes.  In the scur animal, normal horn growth is replaced by small, loose boney growths that are not attached to the skull.  In addition, cranial frontal bones undergo premature fusion (coronal suture synoptosis).  The scur phenotype shows considerable variation between individuals, although in male animals the boney growths tend to be larger than in female animals.  DNA studies in Charolais animals identified a heterozygous mutation in the TWIST1 gene as being responsible for the scur phenotype.  As no homozygous mutant animals were seen, it was assumed that the homozygous condition was embryo lethal.  The TWIST1 gene codes for a transcription factor important for differentiating embryonic mesoderm tissues.  TWIST1 gene expression is important for normal bone growth by regulating osteogenic stem cell proliferation and osteoblast differentiation.  Additional DNA studies in four herds of an extended Charolais pedigree revealed that the same mutation in the TWIST1 gene is also responsible for a congenital abdominal hernia phenotype, again with dominant heredity.  The penetration of the hernia phenotype may be influenced by modifier genes as well as by environmental factors.

References:

OMIA links:  [1593-9913], [2532-9913]

Grohs C, Boussaha M, Hozé C, Capitan A. (2022) Rare cases of hernia of the linea alba among TWIST1 haploinsufficient Charolais cattle. Anim Genet 53:239-241. [35187669]

He XH, Jiang L, Pu YB, et al. (2021) Progress on genetic mapping and genetic mechanism of cattle and sheep horns. Yi Chuan 43:40-51.  [pm/33509773]

Capitan A, Grohs C, Weiss B, et al. (2011) A newly described bovine type 2 scurs syndrome segregates with a frame-shift mutation in TWIST1. PLoS One 6:e22242. [pm/21814570]

Contributed by: Juliana Bouchard and Audrey Boudreault, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)