Analysis of SCA3/MJD3 gene mutation and genetic polymorphism in a Guangxi family with spinocerebellar ataxia 3
Received date: 2013-06-24
Revised date: 2013-08-01
Online published: 2013-10-25
Autosomal dominant cerebellar ataxias (ADCAs) comprise a group of genetically heterogeneous neurodegenerative disorders among which spinocerebellar ataxia type 3 (SCA3) represents the most common form of SCAs worldwide. The fragments of SCA3/MJD gene,which is the member of family GXPL1,were amplified by polymerase chain reaction (PCR). The PCR products of SCA3/MJD gene were detected with capillary electrophoresis (CE) and sequencing to evaluate the size of CAG repeats, feature in the transmission and the mutation in the family with SCA3 in Guangxi province. The results showed that the exon 10 of the SCA3/MJD gene contains 64—71 CAG repeats in all of the affected individuals and three asymptomatic carriers of the family. The number of the CAG repeats during transmission in the normal individuals carrying CGG allele remains consistent, suggesting that CGG allele could have no effect on intergenerational stability of CAG repeats in normal individuals. In addition, two novel point mutations were identified: IVS9-113 T>C in the intronic region and a missense mutation 220 G>A(Glu>Gly) in the encoding region. These two novel point mutations have not been reported and the effect of the mutations on the phenotype of SCA3 is not clear.
CHANG Rong-Ni YUAN Guang-Zhi TAN Jian-Qiang LAI Qing-Niao MA Jun YANG Yi-Jin SHU Wei HOU Wei YUAN Zhi-Gang . Analysis of SCA3/MJD3 gene mutation and genetic polymorphism in a Guangxi family with spinocerebellar ataxia 3[J]. Hereditas(Beijing), 2013 , 35(11) : 1300 -1306 . DOI: 10.3724/SP.J.1005.2013.01300
[1]Bettencourt C, Lima M. Machado-Joseph Disease: from first descriptions to new perspectives. Orphanet J Rare Dis, 2011, 6: 35. <\p>
[2]Dong Y, Sun YM, Wu ZY. The importance of deep explo-ration into clinical heterogeneity of spinocerebellar ataxia type 3. J Neurol Sci, 2013, 326(1/2): 122. <\p>
[3]Shinsuke F, Christina S, Zbigniew KW. Autosomal domi-nant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics. Orphanet J Rare Dis, 2013, 8(1): 14–23. <\p>
[4]Lima M, Costa MC, Montiel R, Ferro A, Santos C, Silva C, Bettencourt C, Sousa A, Sequeiros J, Coutinho P, Maciel P. Population genetics of wild-type CAG repeats in the Machado-Joseph disease gene in Portugal. Hum Hered, 2005, 60(3): 156–163. <\p>
[5]Igarashi S, Takiyama Y, Cancel G, Rogaeva EA, Sasaki H, Wakisaka A, Zhou YX, Takano H, Endo K, Sanpei K, Oyake M, Tanaka H, Stevanin G, Abbas N, Dürr A, Rogaev EI, Sherrington R, Tsuda T, Ikeda M, Cassa E, Nishizawa M, Benomar A, Julien J, Weissenbach J, Wang GX, Agid Y, St George-Hyslop PH, Brice A, Tsuji S. Int-ergenerational instability of the CAG repeat of the gene for Machado-Joseph disease(MJD1)is affected by the genotype of the normal chromosome: implications for the molecular mechanisms of the instability of the CAG repeat. Hum Mol Genet, 1996, 5(7): 923–932. <\p>
[6]Bettencourt C, Silva-Fernandes A, Montiel R, Santos C, Maciel P, Lima M. Triplet repeats: features, dynamics and evolutionary mechanisms. In: Santos C, Lima M, eds. Re-cent Advances in Molecular Biology and Evolution: Ap-plications to Biological Anthropology. Kerala: Research Signpost, 2007: 83–114. <\p>
[7]Maciel P, Gaspar C, Guimarães L, Goto J, Lopes-Cendes I, Hayes S, Arvidsson K, Dias A, Sequeiros J, Sousa A, Rouleau G. A Study of three intragenic polymorphisms in the Machado-Joseph disease gene (MJD1) in relation to genetic instability of the (CAG)n tract. Eur J Hum Genet, 1999, 7(2): 147–156. <\p>
[8]Harding AE. Clinical features and classification of inher-ited ataxias. Adv Neurol, 1993, 61: 1–14. <\p>
[9]谭建强, 汪萍, 胡启平, 李松峰, 舒伟, 马军, 方玲, 华荣, 丁晔, 袁志刚. 广西地区脊髓小脑性共济失调病人的基因诊断和CAG重复扩增. 遗传, 2009, 31(6): 605–610. <\p>
[10]Ichikawa Y, Goto J, Hattori M, Toyoda A, Ishii K, Jeong SY, Hashida H, Masuda N, Ogata K, Kasai F, Hirai M, Maciel P, Rouleau GA, Sakaki Y, Kanazawa I. The ge-nomic structure and expression of MJD, the Machado-Joseph disease gene. J Hum Genet, 2001, 46: 413–422. <\p>
[11]Carvalho DR, La Rocque-Ferreira A, Rizzo IM, Imamura EU, Speck-Martins CE. Homozygosity enhances severity in spinocerebellar ataxia type 3. Pediatr Neurol, 2008, 38(4): 296–299. <\p>
[12]Lerer I, Merims D, Abeliovich D, Zlotogora J, Gadoth N. Machado-Joseph disease: correlation between the clinical features, the CAG repeat length and homozygosity for the mutation. Eur J Hum Genet, 1996, 4(1): 3–7. <\p>
[13]Sobue G, Doyu M, Nakao N, Shimada N, Mitsuma T, Maruyama H, Kawakami S, Nakamura S. Homozygosity for Machado-Joseph disease gene enhances phenotypic severity. J Neurol Neurosurg Psychiatry, 1996, 60(3): 354–356. <\p>
[14]谢秋幼, 梁秀龄, 李洵桦. 国内南方人群遗传性共济失调不同基因亚型的分布状况. 中国临床康复, 2006, 10(12): 161–163. <\p>
[15]张宝荣, 黄鉴政, 夏家辉, 丁美萍, 朱永良, 应智林, 潘乾, 汤熙翔, 姚梅琪. MJD基因CAG不稳定性扩增与临床研究. 遗传, 1999, 21(6): 17–20. <\p>
[16]Cao DH, Liu XL, Qiu GB. Genotyping and prenatal diag-nosis of a large spinocerebellar ataxia pedigree in north-eastern China. J Genet, 2011, 90(2): 369–372. <\p>
[17]Basu P, Chaaopadhyay B, Gangopadhaya PK, Mukherjee SC, Sinha KK, Das SK, Roychoudhury S, Majumder PP, Bhattacharyya NP. Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spi-nocerebellar ataxia patients and distribution of CAG re-peats at the SCA1,
/
| 〈 |
|
〉 |
www.chinagene.cn
备案号：京ICP备09063187号
