Ribonucleases (RNases) catalyze the cleavage and degradation of RNAs in a multitude of cellular processes. RNASET2-deficient leukoencephalopathy is caused by homozygous or compound heterozygous mutations in the human RNASET2 gene, which encodes ribonuclease T2 (RNASET2) – a acidic hydrolase localized in lysosomes. Although the pathomechanism of RNASET2-deficient leukoencephalopathy still remains to be elucidated, it is assumed that the loss of RNASET2 function leads to an accumulation of RNA metabolites that are delivered to lysosome for degradation.
The accumulation of RNAs may interfere with lysosome function. Mutations in the RNASET2 gene associated with RNASET2-deficient leukoencephalopathy are often located in structurally important regions of the RNASET2 protein. Homozygote mutations that has been described so far are: 550 T > C, 87-1341_147 + 1181del2583, 262–2 A>G, 332 + 1delG, c.550 T > C/p.Cys184Arg c.2delT/p.Met1?, c.233C > A. Compound heterozygote mutations are: 50_64del 567G4A, c.397_399delAAG/p.Lys133del, c.145G T/p.Glu49.
Clinical and neuroradiological features of RNASET2-deficient leukoencephalopathy are similar to congenital cytomegalovirus (CMV) brain infection and AGS. Confirmation of the clinical diagnosis can be given via genetic testing of the RNASET2 gene.