김종원 (성균관대학교) | 한빛사논문 > 한빛사

한빛사논문

조회4,476

성균관대학교

CV File 22 kb

Am. J. Hum. Genet., electronically published June 29, 2007 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)

Abstract

Hee-Jin Kim, Kwang-Min Sohn, Michael E. Shy, Karen M. Krajewski, Miok Hwang, June-Hee Park, Sue-Yon Jang, Hong-Hee Won, Byung-Ok Choi, Sung Hwa Hong, Byoung-Joon Kim, Yeon-Lim Suh, Chang-Seok Ki, Soo-Youn Lee, Sun-Hee Kim, and 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.)

Received March 15, 2007; accepted for publication April 26, 2007; electronically published June 29, 2007.

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.

논문정보

형식Research article
게재일2007년 06월 (BRIC 등록일 )
연구진국내(교신)+국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기