Journal article
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)
American journal of human genetics, Vol.81(3), pp.552-558
09/2007
DOI: 10.1086/519529
PMCID: PMC1950833
PMID: 17701900
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.
Details
- Title: Subtitle
- 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)
- Creators
- Hee-Jin Kim - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Kwang-Min Sohn - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Michael E. Shy - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Karen M. Krajewski - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Miok Hwang - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)June-Hee Park - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Sue-Yon Jang - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Hong-Hee Won - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Byung-Ok Choi - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Sung Hwa Hong - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Byoung-Joon Kim - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Yeon-Lim Suh - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Chang-Seok Ki - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Soo-Youn Lee - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Sun-Hee Kim - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)Jong-Won Kim - From the Departments of Laboratory Medicine and Genetics (H.-J.K.; C.-S.K.; S.-H.K.), Otorhinolaryngology and Head & Neck Surgery (S.H.H.), Neurology (B.-J.K.), and Pathology (Y.-L.S.) and Samsung Biomedical Research Institute (K.-M.S.; M.H.; J.-H.P.; Y.J.; H.-H.W.), Samsung Medical Center, Sungkyunkwan University School of Medicine, and Department of Neurology, Ewha Woman's University Medical Center, Ewha Womans University School of Medicine (B.-O.C.), Seoul; and Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI (M.E.S.; K.M.K.)
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.81(3), pp.552-558
- Publisher
- The American Society of Human Genetics
- DOI
- 10.1086/519529
- PMID
- 17701900
- PMCID
- PMC1950833
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Alternative title
- Mutant PRPS1 Gene Causes CMTX5
- Language
- English
- Date published
- 09/2007
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020766002771
Metrics
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