RUNX2 Repeat Expansion Testing
Description
The RUNX2 gene contains an N-terminal stretch of 23 uninterrupted glutamine residues (polyQ) followed by 17 uninterrupted alanine residues (polyA), with a single glutamic acid spacing between them (E), known as the Q/A domain. Pathogenic alanine repeat expansions within the RUNX2 gene have been associated with autosomal dominant cleidocranial dysplasia. Expansions in the polyA tract or the polyQ tract cause loss of transactivation potential of the RUNX2 protein and/or form protein aggregates.
Pathogenicity is dependent upon GCN repeat length according to the following ranges 1-3:
Normal Alleles | Mutable Normal Alleles | Intermediate or Uncertain Alleles | Reduced Penetrance Alleles | Full Penetrance Alleles |
18 | - | 19 | - | 20 or more |