Molecular characteristics

The spectrum of SOX6 variants ranged from balanced chromosomal translocations to partial or complete gene deletions, and to nonsense, missense and other SNVs. SOX6 variants inactivate one SOX6 allele and thus cause a disease that reveals SOX6 haploinsufficiency. These variants were microdeletions and frameshift and nonsense variants. In addition, missense variants in the HMG domain inactivate the protein made from the SOX6 carrier allele. This was supported both by in vitro functional assays and by evidence that many variants in the HMG domain have been shown in other SOX genes to cause SOXopathies.