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

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611122 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Molecular basis: Jacinto et al. (2022) propose that a dominant de novo mutation in the ANKRD28 gene is the causal variant in the single reported calf. "This heterozygous variant at chr1:152807533C>CA represents a 1‐bp insertion in exon 2 of the ANKRD28 gene that directly affect the translation initiation (start) codon (XM_024989836.1: c.2dupT; ...). The predicted consequence of this start‐lost variant is that amino acid Met1 is converted to Leu after activation of an upstream translation initiation site at cDNA position −20, resulting in N‐terminal protein extension by insertion of six amino acids between Met1 and Gly2 (XP_024845604.1: p.Met1_Gly2insIleValGlyGlyLysAlaLeu)." The authors conclude that as "this is a single case study and we have no functional confirmation, this result must be considered preliminary and should be interpreted with caution."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Jacinto et al. (2022): "A 3.5‐month‐old, female, purebred Holstein calf was reported because of its short stature, protruding scapulohumeral joints, increased concavity of the frontal bone, and bossing of the intercornual prominence ...."

Breed: Holstein Friesian (Cattle) (VBO_0000239).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below