Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614335 (trait) , 160794 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0044682: MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome

Mendelian trait/disorder: yes

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: Arthrogryposis, distal, type 1B

Species-specific description: Illustrating the enormous power of genomic tools, Wiedemar et al. (2015) were able to identify a likely causal mutation for a previously unrecorded disease phenotype in just a single calf.

Molecular basis: Wiedemar et al. (2015) reported a likely causal mutation: "a SNP replacing a thymine by a guanine on bovine chromosome 5 at bp-position 65,787,153. It was clearly identified as a de novo mutation as it was absent in both parents, but present in the calf . . . . Interestingly, this SNP situated in exon 13 of the myosin binding protein C slow type (MYBPC1) gene at position 885 of the open reading frame (c.885T>G) is predicted to lead to an amino acid exchange from leucine to arginine of the encoded MYBPC1 protein sequence at position 295 (p.Leu295Arg)".

Clinical features: The single known case was described by Wiedemar et al. (2015) as "A 2-week-old female calf was referred to the Clinic for Ruminants at the Vetsuisse Faculty, University of Berne, Switzerland, with difficulty standing and muscle tremors since birth. Prior treatment by the private veterinarian with selenium, calcium, magnesium, and vitamins had not led to any improvement. The general status at arrival to the clinic was slightly reduced, though the calf was alert and attentive, and tachycardia (152/min) and tachypnea (80/min) were noticeable. Examination of the skin revealed an infected lesion on the fetlock of the left forelimb and several superficial lesions. Gastrointestinal, respiratory, and urinary tracts were without important abnormalities. The musculoskeletal system was normally developed, no atrophy was noticed, but the calf remained in a recumbent position unless lifted up and helped to stand. When standing, it showed tremor, ataxia, and could only move backward with hypermetria in the hind limbs and tip-toe-standing of the front limbs (Fig 1). Consciousness was normal but the calf was unable to orientate itself in its surroundings. Cranial nerve examination showed no deficits. Muscle tone was generally increased in the limbs. No painful reaction was noticed upon palpation of the limbs. The spinal reflexes were generally reduced. Sensibility was normal in the neck and shoulder area, but reduced in the limbs. The head and neck could be moved in all directions and the ears were symmetrical and loose. The clinical signs were localized in the peripheral nervous or musculoskeletal system".

Breed: Holstein Friesian (Cattle) (VBO_0000239).
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: