1206 LETTERS TO THE EDITORS References 1. Deuschl G, Bain P, Brin M, Ad Hoc Scientific Committee. Consensus statement of the movement disorder society on tremor. Mov Disord 1998;13:2–23. 2. Kim M-C, Son BC, Miyagi Y, Kang J-K. Vim thalamotomy for Holmes’ tremor secondary to midbrain tumour. J Neurol Neurosurg Psychiatry 2002;73:453– 455. 3. Shepherd GM, Tauboll E, Bakke SJ, Nyberg-Hansen R. Midbrain tremor and hypertrophic olivary degeneration after pontine hemorrhage. Mov Disord 1997;12:432– 437. 4. Samie MR, Selhorst JB, Koller WC. Post-traumatic midbrain tremors. Neurology 1990;40:62– 66. 5. Pezzini A, Zavarise P, Palvarini L, Viale P, Oladeji O, Padovani A. Holmes’ tremor following midbrain Toxoplasma abscess: clinical features and treatment of a case. Parkinsonism Relat Disord 2002; 8:177–180. 6. Paviour DC, Jager HR, Wilkinson L, Jahanshahi M, Lees AJ. Holmes tremor: application of modern neuroimaging techniques. Mov Disord 2006;21:2260 –2262. 7. Tyler KN. Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret’s. Herpes 2004;11(S2):57A– 64A. 8. Tyler KL, Tedder DG, Yamamoto LJ, Klapper JA, Ashley R, Lichtenstein KA, Levin MJ. Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid. Neurology 1995;45:2246 –2250. 9. Yamamoto K, Chiba HO, Ishitobi M, Nakagawa H, Ogawa T, Ishii K. Acute encephalopathy with bilateral striatal necrosis: favourable response to corticosteroid therapy. Eur J Paediatr Neurol 1997;1:41– 45. 10. Roselli F, Russo I, Fraddosio A, Aniello MS, De Mari M, Lamberti P, Livrea P, Defazio G. Reversible Parkinsonian syndrome associated with anti-neuronal antibodies in acute EBV encephalitis: a case report. Parkinsonism Relat Disord 2006;12:257–260. 11. Dimova PS, Bojinova V, Georgiev D, Milanov I. Acute reversible parkinsonism in Epstein–Barr virus-related encephalitis lethargicalike illness. Mov Disord 2006;21:564 –566. 12. Ohye C, Shibazaki T, Hirai T, et al. Special role of the parvocellular red nucleus in lesion-induced spontaneous tremor in the monkeys. Behav Brain Res 1988;28:241–243. 13. Deuschl G, Wilms H, Krack P, Wurker M, Heiss WD. Function of the cerebellum in Parkinsonian rest tremor and Holmes’ tremor. Ann Neurol 1999;46:126 –128. 14. Remy P, de Recondo A, Defer G, et al. Peduncular ‘rubral’ tremor and dopaminergic denervation: a PET study. Neurology 1995 45:472– 477. 15. Akkus DE, Diramali AB. Postischemic delayed Holmes’ tremor responding to low-dose Cabergoline. Mov Disord 2006;21:733–734. Novel SGCE Gene Mutation in a Korean Patient With Myoclonus–Dystonia With Unique Phenotype Mimicking Moya–Moya Disease Myoclonus– dystonia syndrome (MDS; OMIM 159900) is an autosomal dominant movement disorder characterized by alcohol-responsive myoclonus and dystonia and known to be associated with mutations in the ⑀-sarcoglycan gene (SGCE) on Published online 29 March 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21093 Movement Disorders, Vol. 22, No. 8, 2007 chromosome 7q21.1,2 Recently, several novel type of SGCE mutations were also found.3,4 We report a Korean MDS family with a novel splicing mutation (IVS1⫹1G⬎T) of SGCE and a unique phenotype including bilateral carotid artery stenosis mimicking Moya–Moya disease. The proband, a 45-year-old woman, was hospitalized with complaints of involuntary jerking movements of the neck, trunk, and both arms since the age of 4, and torticollis to the left since the age of 10. At the age of 34, she began to experience seizure-like episodes usually lasting for a few minutes and sometimes causing loss of consciousness and motor aphasia. Ictal or interictal electroencephalograms (EEG) were normal, unlike other reported cases of MDS combined with epilepsy.5 Neurological examination of the proband showed myoclonic jerks affecting mostly axial muscles and a left torticollis. These movements were aggravated by action or stress and improved by alcohol. A cerebral angiogram revealed moderate to severe focal stenosis of bilateral internal carotid arteries with collateral circulation from middle meningeal artery compatible with Moya–Moya disease (Fig. 1). Right cerebral revascularization procedures aborted the seizure-like episodes without the symptomatic improvement of myoclonus– dystonia. We discovered nine affected family members of the proband by direct observation or telephone interview: a great-grandmother (I:2), two siblings (IV:8 and IV:11), two cousins (IV:1 and IV:3), three nephews (V:4, V:6, and V:7), and a niece (V:9) of the proband (IV:14) all had similar symptoms of myoclonus– dystonia (Fig. 2). From the evidence that her deceased grandfather (II:1), father (III:3), and an elder uncle (III:1) were heavy drinkers and died of alcoholic liver diseases, they might have suffered from alcohol-responsive myoclonus. After obtaining informed consent, genomic DNA of the proband and all of her siblings (Fig. 2) was isolated from the peripheral leukocyte. All coding exons and their flanking intronic regions of the SGCE were amplified by the polymerase chain reaction (PCR) and sequenced using the primer sets designed by the authors (available on request). After identification of a novel variation in the splicing donor site of intron 1, two pairs of primers for reverse transcription–PCR (RT-PCR) were designed to demonstrate possible intron retention (Ex1F1, 5⬘-GCTGGGAGGGAAGAAGAAAG-3⬘; In1-R, 5⬘-GGGATGTTGGGAACAGGAAT-3⬘) or exon skipping (Ex1-F2, 5⬘-CACTGGCACATTCTTGCTGA-3⬘; Ex3-R, 5⬘-ATCCAGGTCGGTCTGGGTAA-3⬘). Direct sequencing analysis of the SGCE gene revealed a nucleotide change in the consensus sequence of the splicing donor site of intron 1 (c.108⫹1G⬎T; Fig. 3A). Aberrant splicing of SGCE mRNA isolated from cultured skin fibroblasts was confirmed by the observation of an abnormal RT-PCR amplicon (Fig. 3B, lane P1) resulting from the retention of intron 1 while there was no band with control RNA (lane C1). MR angiography in two siblings of the proband with the same mutation (IV:8 and IV:11), which was performed to verify the possible correlation between the novel splicing mutation of the SGCE gene and carotid artery stenosis, showed no abnormalities (data not shown). In conclusion, we report a Korean MDS family with a novel splicing mutation of the SGCE gene and a unique phenotype that included bilateral carotid artery stenosis mimicking Moya– Moya disease. Since none of the other affected mutation carriers have Moya–Moya disease, it may be coincidental and not LETTERS TO THE EDITOR 1207 FIG. 1. Cerebral angiogram in the proband. FIG. 2. Pedigree of the family with myoclonus– dystonia syndrome. Circle, female; square, male; black symbol, affected; gray symbol, probably affected; open symbol with question mark, possibly affected by history; diagonal line, deceased. Jong-Hun Kim, MD Gyeong-Moon Kim, MD, PhD Department of Neurology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul, South Korea *E-mail: wylee@smc.samsung.co.kr Chang Seok Ki, MD, PhD In-Suk Kim, MD Department of Laboratory Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Seoul, South Korea References FIG. 3. A: Direct sequencing analysis of the SGCE. B: RT-PCR of mRNA isolated from cultured skin fibroblast. C1 (control) and P1 (proband), RT-PCR with Ex1-F1 and In1-R primers; C2 (control) and P2 (proband), RT-PCR with Ex1-F2 and Ex3-R. M, 100 bp size marker. related to the SGCE mutation or the MDS. However, further study is needed to determine whether an association exists. Eun Joo Chung, MD Won Yong Lee, MD, PhD* Ji-Youn Kim, MD 1. Zimprich A, Grabowski M, Asmus F, et al. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus– dystonia syndrome. Nat Genet 2001;29:66 – 69. 2. Nygaard TG, Raymond D, Chen C, et al. Localization of a gene for myoclonus– dystonia to chromosome 7q21– q31. Ann Neurol 1999; 46:794 –798. 3. Valente EM, Edwards MJ, Mir P, et al. The epsilon-sarcoglycan gene in myoclonic syndromes. Neurology 2005;64:737–739. 4. Asmus F, Salih F, Hjermind LE, et al. Myoclonus– dystonia due to genomic deletions in the epsilon-sarcoglycan gene. Ann Neurol 2005;58:792–797. 5. Foncke EM, Klein C, Koelman JH, et al. Hereditary myoclonus– dystonia associated with epilepsy. Neurology 2003;60:1988 –1990. Movement Disorders, Vol. 22, No. 8, 2007