All variants reported thus far cluster within the within the first mono-functional DNA-alkylating methyl methanesulfonate (MMS1) domain of DDB1 (Figure 2), and interestingly, we observed one recurrent protein change in four individuals, c.637G>A (GenBank: NM_001923.4) (p.Glu213Lys [GenBank: NP_001914.3]), and two different substitutions at the same residue, p.Arg188Trp and p.Arg188Gln. All variants were missense except one in-frame deletion at the intron 4-exon 5 boundary. Immunoblot analysis in this patient showed no noticeable change in protein levels. The mutation mechanism is not currently understood.
Cells derived from affected individuals have altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage.
DDB1