In other species: macaques

Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 160500 (trait) , 160760 (gene) , 613426 (trait) , 192600 (trait) , 608358 (trait) , 181430 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific name: Campus syndrome

Species-specific description: The Campus syndrome is a hereditary progressive high-frequency tremor that occurred among the progeny of a clinically normal German Pietrain boar named Campus, which was used in artificial insemination in southern Germany. In 1988, the boar was transferred to the Hanover School of Veterinary Science, Germany, where the disorder has been intensively studied (Schulze, 1993; Richter et al., 1995; Schulze et al., 1996; Tammen et al., 1997). [Compiled by Imke Tammen]

Inheritance: The disorder is autosomal dominant, but the founder boar is normal. It appears, therefore, that the disorder arises from a germline mutation in Campus. [Compiled by Imke Tammen]

Mapping: In an abstract, Tammen and Harlizius (1996) reported having mapped Campus syndrome to chromosome SSC7q. Tammen et al. (1999) reported the details of this mapping, involving a genome scan with 254 microsatellites thta located the Campus gene in a 8cM region of SSC7q. Tammen et al. (1999) noted that this region of SSC7 corresponds to a portion of human chromosome HSA14 and that a human disorder homologous to Campus syndrome, namely dominant distal myopathy type 1 (MPD1), maps to this region of HSA14.

Molecular basis: The discovery by Meredith et al. (2005; Am. J. Hum. Genet. 75: 703-708) that the molecular basis of human MPD1 is a range of mutations in the myosin heavy-chain gene (MYH7), suggested a strong comparative candidate gene for Campus syndrome. When the porcine genome assembly became available, Murgiano et al. (2012) checked that the porcine MHY7 gene is located in the Campus region and then, by sequencing affected animals, identified "an in-frame insertion within exon 30 of MYH7 (c.4320_4321insCCCGCC) which was perfectly associated with the disease phenotype. . . . The mutation is predicted to insert two amino acids (p.Ala1440_Ala1441insProAla) in a very highly conserved region of the myosin tail."

Clinical features: Affected piglets are normal at birth. The first clinical signs become evident from 2 to 9 weeks of age: a muscular tremor (first in the hind quarters, and later in the forequarters) is observed when the piglets are standing or moving. At rest, the tremor ceases immediately. Within a few weeks, the tremor becomes more pronounced, and the animals are quickly exhausted. They continue to feed, drink and grow normally, except that feed consumption is increased. Plasma lactate levels are increased and body temperature is elevated to 40-41 degrees C. Affected piglets are susceptible to stress and thus their life expectancy is reduced to 3-18 months. Richter et al. (1995) tested several drugs (propranolol, clonazepam, primidone, phenobarbital, biperiden, clozaoine) but none was capable of attenuating the syndrome. Neurophysiological studies revealed a rhythmic 14- to 15-Hz tremor. Ulnar motor nerve conduction velocity is normal. [Compiled by Imke Tammen]

Pathology: Schulze et al. (1996) observed disseminated and grouped angular atrophy of both muscle fiber types (but predominantly type I muscle fibers), small dark fibers, nuclear clumps and occasionally target fibers and moth-eaten fibers. These alterations indicate a denervation atrophy. Transmission electron microscopy revealed that at neuromuscular junctions, occasionally axon terminals are separated from the primary synaptic clefts. Examination of brain, spinal cord and peripheral nerve showed no macroscopical or histopathological alterations. [Compiled by Imke Tammen]

Breed: Pietrain (Pig) (VBO_0001189).
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: