Categories: Skeleton phene (incl. short stature & teeth)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 103320 (gene)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive lethal

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2011

Species-specific name: Bovine Hereditary Arthrogyposis Multiplex Congentia

Species-specific symbol: BHAC

Species-specific description: Also known as Curly Calf Syndrome

History: The first case in the USA was reported to Dr David Steffen (University of Nebraska) in 2002. The next report was in 2006, followed by an increasing number in the following years. By September, 48 cases had been reported to Dr Jon Beever, who subsequently developed a DNA test.

Molecular basis: Deletion: a 23,363 bp deletion "encompasses the entirety of the ISG15 ubiquitin-like modifier (ISG15) gene . . . one or both of the 5' regulatory region of the hairy and enhancer split 4 (HES4) and of the agrin (AGRN) gene and of the first two exons of the AGRN gene" (Beever and Marron, 2011)

Clinical features: In the words of Dr David Steffen, in an article posted on the AAA website on 5th September 2008, "The spine is bent and twisted in affected calves. The calves are small and appear thin due to limited muscle development. Legs are often rigid and may be hyperextended {common in rear limbs) or contracted. In some cases the rigid limbs result in calving difficulties." [http://www.angus.org/index.html; accessed 14 October 2008]

Genetic testing: The causal mutation described above, upon which a DNA test is based, was patented in 2009 and published in 2011 (Beever and Marron, 2011).

Breed: Angus (Cattle) (VBO_0000104).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: