SHORT REPORT ABSTRACT: Distal myopathy with rimmed vacuoles (DMRV) is an early- adult-onset, distal myopathy caused by a mutation of the UDP-N-acetylglu- cosamine 2 epimerase/N-acetylmannosamine kinase (GNE) gene. We herein report four Thai patients with DMRV who carried compound heterozy- gous mutations of the GNE gene including three novel (p.G89R, p.P511T, and p.I656N) and two known mutations (p.A524V and p.V696M). All patients shared p.V696M in one allele. Our study demonstrates the mutation spec- trum of the GNE gene in Thai patients with DMRV. Muscle Nerve 34: 775–778, 2006 MUTATION ANALYSIS OF THE GNE GENE IN DISTAL MYOPATHY WITH RIMMED VACUOLES (DMRV) PATIENTS IN THAILAND TEERIN LIEWLUCK, MD, 1 THEERAPHONG PHO-IAM, BSc, 2 CHANIN LIMWONGSE, MD, 2 WANNA THONGNOPPAKHUN, PhD, 2 KANOKWAN BOONYAPISIT, MD, 3 NATTE RAKSADAWAN, MD, 4 KUMIKO MURAYAMA, BSc, 5 YUKIKO K. HAYASHI, MD, PhD, 5 ICHIZO NISHINO, MD, PhD, 5 and TUMTIP SANGRUCHI, MD 1 1 Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Prannok Rd., Siriraj, Bangkok-Noi, Bangkok 10700, Thailand 2 Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 3 Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand 4 Bangkok Neuroscience Center, Bangkok International Hospital, Bangkok, Thailand 5 Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan Accepted 21 April 2006 Distal myopathy with rimmed vacuoles (DMRV) is a clinicopathologically distinct distal myopathy with autosomal-recessive inheritance. It is characterized clinically by preferential weakness of the tibialis an- terior muscle and sparing of the quadriceps femoris muscle, with the age of onset ranging from 15– 40 years (mean, 26 years). 7 Patients become wheelchair- bound between 26 and 57 years of age, on average 12 years after the onset of symptoms. 7 Serum creatine kinase (CK) level is normal or mildly elevated. On modified Gomori trichrome staining, muscle biopsy typically shows numerous empty-looking vacuoles with eosinophilic rimming or so-called rimmed vacu- oles (RV). These pathognomonic RV are commonly seen in atrophic fibers. Necrotic and regenerating fibers are uncommon. Unusual inflammatory cell infiltration mimicking sporadic inclusion-body myo- sitis (sIBM) can be found. 11 DMRV is known to be the same disease as hered- itary inclusion-body myopathy (HIBM), which was originally reported as quadriceps-sparing myopathy. 1 DMRV/HIBM is caused by mutations in the GNE gene encoding UDP-N-acetylglucosamine 2 epimer- ase/N-acetylmannosamine kinase, a bifunctional en- zyme in the sialic acid synthetic pathway. 2 Geneti- cally confirmed cases of DMRV/HIBM have been found in Iranian Jews, Japanese, Koreans, Chinese, Americans, and Europeans. However, no case has been reported from Southeastern Asian countries, so far as we are aware. Herein, we report four unre- lated Thai patients with DMRV confirmed both clini- copathologically and genetically. MATERIALS AND METHODS Patients. We studied patients who fulfilled the fol- lowing diagnostic criteria of DMRV: (1) autosomal- recessive or sporadic inheritance; (2) early-adult onset; (3) preferential weakness of tibialis anterior Abbreviations: ATPase, adenosine triphosphatase; CK, creatine kinase; DMRV, distal myopathy with rimmed vacuoles; GNE, UDP-N-acetylglu- cosamine 2 epimerase/N-acetylmannosamine kinase; H&E, hematoxylin and eosin; HIBM, hereditary inclusion-body myopathy; PAS, periodic acid–Schiff; RV, rimmed vacuoles; sIBM, sporadic inclusion-body myositis Key words: distal myopathy with rimmed vacuoles; DMRV; GNE; hereditary inclusion-body myopathy; UDP-N-acetylglucosamine 2 epimerase/N-acetyl- mannosamine kinase Correspondence to: T. Liewluck; e-mail: teerinl@gmail.com © 2006 Wiley Periodicals, Inc. Published online 29 June 2006 in Wiley InterScience (www.interscience.wiley. com). DOI 10.1002/mus.20583 Short Reports MUSCLE & NERVE December 2006 775