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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 166210 (trait) , 259420 (trait) , 166220 (trait) , 120160 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2001

Cross-species summary: Abnormally brittle bones that fracture easily due to variants in the COL1A2 gene.

Species-specific symbol: OI

Molecular basis: Campbell et al. (2001) reported a likely causal variant in an affected Beagle as: "a mutation in which nucleotides 3991-3994 ("CTAG") were replaced with "TGTCATTGG." The first seven bases of the inserted sequence were identical to nucleotides 4002-4008 of the normal canine COL1A2 sequence. The resulting frameshift changed 30 amino acids and introduced a premature stop codon." In an affected Chow Chow, Quist et al. (2017) identified a likely causal variant as "a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936+1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates." Letko et al. (2019) reported a "de novo in‐frame duplication in the COL1A2 gene [g.19898279_19898281dup; c.877_879dupCCC] in a Lagotto Romagnolo dog with osteogenesis imperfecta". The de novo nature of the variant was concluded from the observation that "both parents, as well as all four littermates, were homozygous wild type . . . . An additional 87 unrelated Lagotto Romagnolo dogs were genotyped homozygous wild type, which confirmed the presence of variant allele only in the single affected dog."

Breeds: Beagle (Dog) (VBO_0200131), Chow Chow (Dog) (VBO_0200361), Lagotto Romagnolo (Dog) (VBO_0200804).
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: