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

Possibly relevant human trait(s) and/or gene(s) (MIM number): 610393 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific description: FN thanks Hubert Pausch for advice on updating this entry.

History: This form of proportionate dwarfism in Fleckvieh cattle was first reported by Gottwald (1967).

Mapping: In a preprint posted on the Cold Spring Harbor bioRxiv preprint server on 15th January 2016, Schwarzenbacher et al. (2016) reported mapping this autosomal recessive disorder to a "1.85 Mb segment (14.88 Mb – 16.73 Mb)" segment of chromosome BTA3. A peer-reviewed version of this paper (by the same authors; see list below) was published on 31 March.

Molecular basis: In a preprint posted on the Cold Spring Harbor bioRxiv preprint server on 15th January 2016, Schwarzenbacher et al. (2016) documented the likely causal mutation as a 1bp frameshift deletion on chromosome BTA3: rs723240647, g.15079217delC, ENSBTAT00000027126:c.4285_4287delCCCinsCC, p.Glu1430LysfsX66 in exon 20 of the GON4L gene. A peer-reviewed version of this paper (by the same authors; see list below) was published on 31 March.

Clinical features: As reported by Schwarzenbacher et al. (2016): "Twenty-seven calves (16 males and 11 females) with strikingly low birth weight (~15kg) and size despite normal gestation length were noticed among the descendants of an artificial insemination bull. Four affected calves were clinically and pathologically examined. At age 61, 97, 101 and 143 days, they were underweight at 42, 79, 53 and 51 kg, respectively. The calves had multiple craniofacial aberrations (i.e., brachygnatia inferior, elongated narrow heads, structural deformities of the muzzle) and spinal distortions. Wrinkled skin, areas with excessive skin and a disproportionately large head became evident during rearing . . . . Although the general condition, feed intake and locomotion of the animals were normal, their growth remained restricted. The average weight gain of an affected animal during a hospitalisation period of 400 days was only 450 g per day, i.e. less than half the weight gain of healthy Fleckvieh bulls."

Breed: Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: