Mutations in the a-synuclein gene in Parkinson's disease among Indians NagarS,JuyalRC,ChaudharyS,BehariM,GuptaM,RaoSN,Thelma BK. Mutations in the a-synuclein gene in Parkinson's disease among Indians. Acta Neurol Scand 2001: 103: 120±122. # Munksgaard 2001. Objective ±ToinvestigatetheprevalenceofG88C,G209Aandanyother mutations) in exons 3 and 4 of the a-synuclein gene in Indian patients with Parkinson's disease PD). Methods ± A total of 169 PD patients comprising 18 familial, 3 juvenile, 48 early onset and 100 sporadic cases were included in this study. Genomic DNA was ampli®ed by PCR using primersspeci®cforExons3and4.MutationsatG88CandG209Awere screened following restriction enzyme digestion of the PCR product. Direct PCR product sequencing of entire exons 3 and 4 was carried out foratleastoneprobandeachfromthe10familialcases. Results ±Neither G88C and G209A mutations nor any other mutation in exons 3 and 4 was found in the PD patients analysed. Conclusion ± The G88C and G209A mutations do not seem to be the predominant genetic determinant of PD among Indians. S. Nagar 1 , R. C. Juyal 2 , S. Chaudhary 1 , M. Behari 3 , M. Gupta 4 ,S.N.Rao 5 , B. K. Thelma 1 1 Department of Genetics, University of Delhi South Campus, New Delhi, 2 National Institute of Immunology, New Delhi, 3 Department of Neurology, All India Institute of Medical Sciences, New Delhi, 4 Department of Neurology, Gobind Ballabh Pant Hospital, Delhi, 5 Department of Neurology, Kasturba Gandhi Medical College Hospital, Manipal, Karnataka Key words: Parkinson's disease; a-synuclein gene; G209A mutation; G88C mutation; Indian population Dr B. K. Thelma, Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India Tel.: 91 11 4678201 Fax: 91 11 6885270 e-mail: humgen@del3.vsnl.net.in Accepted for publication October 6, 2000 Parkinson's disease PD) is characterized by degeneration of dopaminergic neurons in the substantia nigra in the midbrain. It affects about 1.6% of those above 60 years of age 1). Crude prevalence rates for PD in different states of India are 7 per 100,000 in rural Karnataka in southern India 2) and 14.1 per 100,000 in rural Kashmir in northern India 3). In the latter study, age adjusted prevalenceforpeopleabove50yearsofagewas134 per100,000.Aslightlyhigherprevalencerateof192 per 100,000 was found among closely bred Parsi community from Bombay 4). Although the pri- mary cause of PD remains unidenti®ed genetic factors seem to contribute considerably to the etiology of PD. Todate, two different mutations in the a-synuclein gene namely a G to A missense mutationAla53Thr)atposition209inexon4ina large Italian family and three smaller Greek kindreds 5), and a novel G to C missense mutation Ala 30 Pro) at position 88 in exon 3 in a family of Germanorigin6),allwithautosomaldominantPD have been reported. These observations raised the possibility that these mutations in the a-synuclein gene may be responsible for a signi®cant number of familial PD cases and could be an effective molecular diagnostic tool. However, several recent studies among PD patients from different popula- tions7±12)reporttheabsenceofthesemutationsin their study samples. There is no report on a- synuclein gene and mutations), if any, in PD among Indians. Therefore, we have undertaken this studytoinvestigatetheprevalenceofG88C,G209A and any other mutations) in exons 3 and 4 of a- synuclein gene not only in familial cases but also in all forms of PD including juvenile, early onset and sporadic PD among Indians.The samples analysed comprised patients from different states of the country including Karnataka, Tamil Nadu, Acta Neurol Scand 2001: 103: 120±122 Printed in UK. All rights reserved Copyright # Munksgaard 2001 ACTA NEUROLOGICA SCANDINAVICA ISSN 0001-6314 120