Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2).
Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5).
X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1.