STRs database » RUNX2 locus
Overview of repeats
Polyalanine expansions in exon 3 of the RUNX2 gene (also known as CBFA1) have been associated with the cleidocranial dysplasia (CCD). Mundlos et al. (1997) described a family where six members carried an expanded allele. The repeat size in these patients was 27, whereas the normal length is 17 alanine repeats (Mundlos et al. (1997)).
In 2015, a case study was published reporting on a Japanese patient with CCD who harbored a rare variant of the RUNX2 gene, resulting in an expansion from 17 to 20 alanine residues in the polyalanine tract (c.181_189dupGCGGCGGCT). Subsequent in vitro experiments revealed that the expanded RUNX2 formed intracellular ubiquitinated aggregates and exerted a dominant negative effect. In comparison to a RUNX2 variant with a 10 alanine expansion, it exhibited slower aggregation growth. These findings suggest that the presence of the RUNX2 (+3 Ala) variant was associated with CCD in this particular case, and the accumulation of intracellular aggregates correlated with the length of the alanine tract (Shibata et al. (2016)).