DOI QR코드

DOI QR Code

Distribution of five common subtypes of spinocerebellar ataxia in the Korean population

  • Choi, In-Hee (Medical Genetics Center, Asan Medical Center) ;
  • Kim, Gu-Hwan (Medical Genetics Center, Asan Medical Center) ;
  • Lee, Beom-Hee (Medical Genetics Center, Asan Medical Center) ;
  • Choi, Jin-Ho (Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Medical Genetics Center, Asan Medical Center)
  • 투고 : 2014.12.08
  • 심사 : 2014.12.10
  • 발행 : 2014.12.31

초록

Purpose: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease for which more than 30 subtypes have been identified. However, 5 subtypes, SCA1, SCA2, SCA3, SCA6, and SCA7, account for more than 60% of cases. In this study, we report the distribution of these 5 subtypes in Korean patients. Materials and Methods: Six hundred and thirty-eight unrelated patients with a presumptive diagnosis of SCA were included in this study. Trinucleotide (CAG) repeat number (TNR) repeat number was determined using fluorescently labeled primers and fragment analysis. Results: A total of 128 unrelated patients (20.1% of all individuals tested) tested positive for SCA subtypes, including SCA1 (5 patients, 3.9% of those testing positive), SCA2 (38 patients, 29.7%), SCA3 (30 patients, 23.4%), SCA6 (39 patients, 30.5%), and SCA7 (16 patients, 12.5%). The mean copy number of pathogenic TNR alleles was $45{\pm}8.5$ for SCA1, $42{\pm}3.1$ for SCA2, $72{\pm}5.4$ for SCA3, $23{\pm}1.5$ for SCA6, and $50{\pm}11.4$ for SCA7. TNR copy number was inversely correlated with onset age in SCA2, SCA6, and SCA7. Conclusion: SCA2, SCA3, and SCA6 are common SCA subtypes in Korean patients and could be screened as a first-line test. Expanded pathogenic allele size was associated with early onset age.

키워드

참고문헌

  1. Bird TD. Hereditary Ataxia Overview. [http://www.ncbi.nlm.nih.gov/books/NBK1138/]
  2. Schols L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 2004;3:291-304. https://doi.org/10.1016/S1474-4422(04)00737-9
  3. Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol 2010;9:885-94. https://doi.org/10.1016/S1474-4422(10)70183-6
  4. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007;30:575-621. https://doi.org/10.1146/annurev.neuro.29.051605.113042
  5. Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 2014;42:174-83. https://doi.org/10.1159/000358801
  6. Moseley ML, Benzow KA, Schut LJ, Bird TD, Gomez CM, Barkhaus PE, et al. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998;51:1666-71. https://doi.org/10.1212/WNL.51.6.1666
  7. Saleem Q, Choudhry S, Mukerji M, Bashyam L, Padma MV, Chakravarthy A, et al. Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation. Hum Genet 2000;106:179-87. https://doi.org/10.1007/s004390051026
  8. Storey E, du Sart D, Shaw JH, Lorentzos P, Kelly L, McKinley Gardner RJ, et al. Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. Am J Med Genet 2000;95:351-7. https://doi.org/10.1002/1096-8628(20001211)95:4<351::AID-AJMG10>3.0.CO;2-R
  9. Tang B, Liu C, Shen L, Dai H, Pan Q, Jing L, et al. Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol 2000;57:540-4. https://doi.org/10.1001/archneur.57.4.540
  10. Maruyama H, Izumi Y, Morino H, Oda M, Toji H, Nakamura S, et al. Difference in disease-free survival curve and regional distribution according to subtype of spinocerebellar ataxia: a study of 1,286 Japanese patients. Am J Med Genet 2002;114:578-83. https://doi.org/10.1002/ajmg.10514
  11. Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, et al. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol 2004;61:727-33. https://doi.org/10.1001/archneur.61.5.727
  12. Lee SG, Ki CS, Kim JW, Suh JS. Distribution of alleles and clinical manifestation in patients with progressive ataxia caused by trinucleotide repeat expansion. Korean J Lab Med 2003;23:60-6.
  13. Lee WY, Jin DK, Oh MR, Lee JE, Song SM, Lee EA, et al. Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients. Arch Neurol 2003;60:858-63. https://doi.org/10.1001/archneur.60.6.858
  14. Kim HJ, Jeon BS, Lee WY, Chung SJ, Yong SW, Kang JH, et al. SCA in Korea and its regional distribution: a multicenter analysis. Parkinsonism Relat Disord 2011;17:72-5. https://doi.org/10.1016/j.parkreldis.2010.09.006