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mljgoums 2020, 14(5): 19-24 |
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zakeri M, babaei A H, akbari M T, zare S, khordadpoor F. Prevalence of Trinucleotide Expansions in SCA17/TBP and JPH3 Genes and Octapeptide Insertion in PRNP Gene in Iranian Patients with Huntington-Disease like Syndrome. mljgoums 2020; 14 (5) :19-24
URL: http://mlj.goums.ac.ir/article-1-1241-en.html
URL: http://mlj.goums.ac.ir/article-1-1241-en.html
1- mana Zakeri, Islamic Azad University Tehran medical branch, Department of Biology, Tehran.Iran.
2- Babaei A.H, Science and reserch branch, Islamic Azad University, Tehran, Iran.
3- mohamad taghi Akbari, Tehran medical genetic labratory,Tehran, Iran. ,mtakbari@modares.ac.ir
4- shohreh zare karizi,Department of biology varamin pishva branch, Islamic Azad University.
5- faravarh khordad poor deilamani, Tehran medical genetics laboratory, Tehran, Iran.
2- Babaei A.H, Science and reserch branch, Islamic Azad University, Tehran, Iran.
3- mohamad taghi Akbari, Tehran medical genetic labratory,Tehran, Iran. ,
4- shohreh zare karizi,Department of biology varamin pishva branch, Islamic Azad University.
5- faravarh khordad poor deilamani, Tehran medical genetics laboratory, Tehran, Iran.
Abstract: (2379 Views)
Background and objective: Huntington's disease (HD) is an autosomal dominant disorder that mainly affects adults. Although mutations in the IT15 gene have been known as the main cause of the disease, patients with HD like (HDL) syndrome have mutations in genes other than the IT15 gene. In this study, we investigate the frequency of mutations in SCA17/TBP, JPH3 and PRNP genes in patients with HDL syndrome.
Methods: The frequency of mutations in SCA17/TBP, JPH3 and PRNP genes was studied in 56 patients with HDL phenotype but without trinucleotide expansion in the IT15 gene. DNA was extracted from peripheral whole blood by the salting out method. PCR was performed using specific primers for each gene. PCR products were separated on polyacrylamide gel. Sequencing was performed on some samples to confirm the PCR results.
Results: We found neither trinucleotide expansion in the JPH3 and SCA17, nor octapeptide insertion in the PRNP gene.
Conclusion: Based on the results, Iranian patients with HDL syndrome do not have mutation in the TBP, JPH3 and PRNP genes. However, this result may be due to population differences, rarity of the mutations in the studied genes and the small number of study subjects. Therefore, studies with a larger study population that investigate other mutations, such as point mutations in the mentioned genes may help clarify the exact cause of HDL phenotype in Iranian patients.
Methods: The frequency of mutations in SCA17/TBP, JPH3 and PRNP genes was studied in 56 patients with HDL phenotype but without trinucleotide expansion in the IT15 gene. DNA was extracted from peripheral whole blood by the salting out method. PCR was performed using specific primers for each gene. PCR products were separated on polyacrylamide gel. Sequencing was performed on some samples to confirm the PCR results.
Results: We found neither trinucleotide expansion in the JPH3 and SCA17, nor octapeptide insertion in the PRNP gene.
Conclusion: Based on the results, Iranian patients with HDL syndrome do not have mutation in the TBP, JPH3 and PRNP genes. However, this result may be due to population differences, rarity of the mutations in the studied genes and the small number of study subjects. Therefore, studies with a larger study population that investigate other mutations, such as point mutations in the mentioned genes may help clarify the exact cause of HDL phenotype in Iranian patients.
Research Article: Original Paper |
Subject:
Human Genetics
Received: 2019/08/18 | Accepted: 2019/11/20 | Published: 2020/08/24 | ePublished: 2020/08/24
Received: 2019/08/18 | Accepted: 2019/11/20 | Published: 2020/08/24 | ePublished: 2020/08/24
References
1. Margolis RL, Ross CA. Diagnosis of Huntington Disease. Clinical Chemistry. 2003; 49(10): 1726-1732. [DOI:10.1373/49.10.1726]
2. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014; 10(4): 204-16. [DOI:10.1038/nrneurol.2014.24]
3. Warby SC, Graham RK. huntingtons disessase. Initial posting. 1998.
4. Paucar M, Xiang F, Moore R, Walker R, Winnberg E, Svenningsson P. Genotype-phenotype analysis in inherited prion disease with eight octapeptide repeat insertional mutation. Prion. 2013; 7(6): 501-510. [DOI:10.4161/pri.27260]
5. Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, et al. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. Nat Genet. 2001; 29(4): 377-8. [DOI:10.1038/ng760]
6. Puckett C, Concannon P, Casey C, Hood L. Genomic structure of the human prion protein gene. Am J Hum Genet. 1991; 49(2): 320-329.
7. Stevanin G, Fujigasaki H, Lebre AS, Camuzat A, Jeannequin C, Dode C, et al. Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. Brain 2003; 126(7): 1599-603. [DOI:10.1093/brain/awg155]
8. Margolis RL, Rudnicki DD, Holmes SE. Huntington's Disease like-2: Review and Update. Acta Neurol Taiwan. 2005; 14(1): 1-8.
9. Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Molec Genet 2001; 10: 1441-1448. [DOI:10.1093/hmg/10.14.1441]
10. Imbert G, Trottier Y, Beckmann J, Mandel JL. The gene for the TATA binding protein (TBP) that contains a highly polymorphic protein coding CAG repeat maps to 6q27. Genomics. 1994; 21(3): 667-8.doi: 10.1006/geno.1994.1335. [DOI:10.1006/geno.1994.1335]
11. Shimojo Y, Osawa Y, Fukumizu M, Hanaoka S, Tanaka H, Ogata F, et al. Severe infantile entatorubral pallidoluysian atrophy with extreme expansion of CAG repeats. Neurology. 2001; 56(2): 277-278. [DOI:10.1212/WNL.56.2.277]
12. Schneider SA, Walker RH, Bhatia KP. The huntingtons disease-like syndrome what to consider in patient with a negative huntingtones like disease gene test. Nat Clin Pract Neurol. 2007; 3(9): 517-25.doi: 10.1038/ncpneuro0606. [DOI:10.1038/ncpneuro0606]
13. Puckett C, Concannon P, Casey C, Hood L. Genomic structure of the human prion protein gene. Am J Hum Genet. 1991; 49(2): 320-329.
14. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215-1220. [DOI:10.1093/nar/16.3.1215]
15. Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, et al. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. Nat Genet 2001; 29(4): 377-8. [DOI:10.1038/ng760]
16. Stevanin G, Fujigasaki H, Lebre AS, Camuzat A, Jeannequin C, Dode C, et al. Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. Brain. 2003; 126(7): 1599-603. [DOI:10.1093/brain/awg155]
17. Rodrigues GR, Walker RH, Bader B, Danek A, Brice A, Cazeneuve C, et al. Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype.Arq Neuropsiquiatr. 2011; 69(3): 419-23. doi: 10.1590/S0004-282X2011000400002. [DOI:10.1590/S0004-282X2011000400002]
18. Margolis RL, Holmes SE, Rosenblatt A, Gourley L, Hearn EO, Ross CA. HDL2 in north American and japan. Ann Neural. 2004; 56(5): 570-674. DOI: 10.1002/ana.20248. [DOI:10.1002/ana.20248]
19. Keckarević M, Savić D, Romac S. JP-3 gene polymorphism in a healthy population of Serbia and Montenegr. Journal of Genetics. 2005; 84(1): 69-71. [DOI:10.1007/BF02715892]
20. Schneider SA, Walker RH, Bhatia KP. The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test. Nat Clin Pract Neurol. 2007; 3(9): 517-25. doi: 10.1038/ncpneuro0606. [DOI:10.1038/ncpneuro0606]
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.