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Mutations in PRPS1, Which Encodes the Phosphoribosyl Pyrophosphate Synthetase Enzyme Critical for Nucleotide Biosynthesis, Cause Hereditary Peripheral Neuropathy with Hearing Loss and Optic Neuropathy (CMTX5)
- Source :
- The American Journal of Human Genetics. 81(3):552-558
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- We have identified missense mutations at conserved amino acids in the PRPS1 gene on Xq22.3 in two families with a syndromic form of inherited peripheral neuropathy, one of Asian and one of European descent. 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. The family of European descent was reported in 1967 as having Rosenberg-Chutorian syndrome, and recently a Korean family with the same symptom triad was identified with a novel disease locus CMTX5 on the chromosome band Xq21.32-q24. PRPS1 (phosphoribosyl pyrophosphate synthetase 1) is an isoform of the PRPS gene family and is ubiquitously expressed in human tissues, including cochlea. The enzyme mediates the biochemical step critical for purine metabolism and nucleotide biosynthesis. The mutations identified were E43D, in patients with Rosenberg-Chutorian syndrome, and M115T, in the Korean patients with CMTX5. We also showed decreased enzyme activity in patients with M115T. PRPS1 is the first CMT gene that encodes a metabolic enzyme, shedding a new light on the understanding of peripheral nerve-specific metabolism and also suggesting the potential of PRPS1 as a target for drugs in prevention and treatment of peripheral neuropathy by antimetabolite therapy.
- Subjects :
- Adult
Male
Adolescent
Hearing Loss, Sensorineural
Molecular Sequence Data
Mutation, Missense
Biology
White People
Optic neuropathy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Asian People
Report
Optic Nerve Diseases
Ribose-Phosphate Pyrophosphokinase
medicine
Genetics
Humans
Gene family
Missense mutation
Genetics(clinical)
Amino Acid Sequence
Gene
Genetics (clinical)
030304 developmental biology
Chromosomes, Human, X
0303 health sciences
Nucleotides
Arts syndrome
Phosphoribosyl pyrophosphate
Peripheral Nervous System Diseases
Syndrome
medicine.disease
3. Good health
Peripheral neuropathy
chemistry
Sensorineural hearing loss
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 81
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- The American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....11ff452a36df2d81362135750872c692
- Full Text :
- https://doi.org/10.1086/519529