In other species: sheep

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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 100800 (trait) , 146000 (trait) , 187600 (trait) , 187601 (trait) , 134934 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2020

Inheritance: Häfliger et al. (2020): "Considering that approximately 25% of offspring were affected, we assume that the sire is a germline mosaic for the variant but unfortunately no semen was available to confirm."

Molecular basis: Whole-genome sequencing of an affected calf and both its parents, followed by filtering of variants, enabled Häfliger et al. (2020) to identify a stop-lost mutation in FGFR3 as the likely causal variant, namely g.116,767,863C>A; NM_174318.3: c.2408G>T; [XM_024992994.1: p.(Ter803Leuext*93), which is "predicted to extend the sequence at the C‐terminal end with 93 additional amino acids". This variant resulted from a de novo mutation in the germline of the sire.

Clinical features: This disorder was first described by Drögemüller et al. (2006). As summarised by Häfliger et al. (2020): "a mild shortening of the upper jaw (brachygnathia superior) and an abnormal stature with movement disabilities owing to severe skeletal shortening of the limbs and hyperextension of the joints . . . . Furthermore, an examination of the profound shortened long bones of CD‐affected calves revealed a rarefication of primary spongiosa. Interestingly, there was no indication for irregularly arranged chondrocytes of epiphyseal plates . . . , as reported in other forms of bovine dwarfism or chondrodysplasia."

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: