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PRPS1

MIM.311850 Xq22-q24

Monday 15 October 2007

PRPS1 encodes a component of the phosphoribosyl pyrophosphate synthetase enzyme (PRPS). The enzyme mediates the biochemical step critical for purine metabolism and nucleotide biosynthesis.

Phosphoribosylpyrophosphate synthetase (PRPS ) (EC 2.7.6.1) catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for the de novo and salvage pathways of purine and pyrimidine biosynthesis. Three PRPS genes have been identified: the widely expressed PRPS1 (MIM.311850) and PRPS2 (MIM.311860) genes, which map to chromosome Xq22-q24 and Xp22 respectively, and PRPS3 (PRPS1L1), which maps to chromosome 7 and appears to be transcribed only in testis.

Pathology

- PRPS1 missense mutations at conserved amino acids in the PRPS1 gene on Xq22.3 in hereditary peripheral neuropathy with hearing loss and optic neuropathy (CMTX5), a syndromic form of inherited peripheral neuropathy reported as Rosenberg-Chutorian syndrome.

  • The disease is inherited in an X-linked recessive manner, and the affected male patients invariably develop sensorineural hearing loss of prelingual type followed by gating disturbance and visual loss.
  • PRPS1 is the first CMT gene that encodes a metabolic enzyme.

- PRPS1 superactivity (MIM.300661) is an allelic disorder resulting from increased enzyme activity. Some affected patients have neurologic symptoms, including sensorineural deafness.

- Arts syndrome (MIM.301835) results from loss of PRPS1 activity and has a severe neurologic phenotype including mental retardation, early-onset hypotonia, and susceptibility to infections.

PRPSs

Phosphoribosylpyrophosphate synthetase (PRPSs) (EC 2.7.6.1) catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for the de novo and salvage pathways of purine and pyrimidine biosynthesis.

Three PRPSs genes have been identified: the widely expressed PRPS1 (MIM.311850) and PRPS2 (MIM.311860) genes, which map to chromosome Xq22-q24 and Xp22 respectively, and PRPS3 (PRPS1L1), which maps to chromosome 7 and appears to be transcribed only in testis.

See also

- PRPSs: PRPS1, PRPS2, PRPS3
- X-linked Charcot-Marie-Tooth diseases (CMTXs)

  • CMTX1 (MIM.302800)
  • CMTX2 (MIM.302801)
  • CMTX3 (MIM.302802)
  • CMTX4 (MIM.310490)
  • CMTX5 (MIM.311070)

References

- de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Petersen M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet. 2007 Sep;81(3):507-18. PMID: 17701896