Novel Mutation in FRDA Gene among Iranian Patients with Friedreich's Ataxia
Archives of Advances in Biosciences,
Vol. 11 No. 3 (2020),
26 September 2020
,
Page 30-36
https://doi.org/10.22037/aab.v11i3.31128
Abstract
Introduction: Friedrich Ataxia’s diagnosis is typically based on clinical symptoms and extended GAA repeats. However, in some rare cases the disease is caused as a result of the mutation in the exons of the FRDA (Friedreich's ataxia) gene. The current study aimed to examine point mutations in exon 1 of the FRDA gene with the goal of finding a better way for diagnosing people suspected of this disease.
Materials and Methods: In this study, 30 suspected patients of Friedrich Ataxia underwent PCR molecular test. Subsequently, sequencing and long PCR were utilized to assess exon 1 in five patients with extended repeats.
Results: In total, 25 participants who had extended repeats were diagnosed with Friedrich Ataxia. In one out of the five patients, the nucleotide change from G to T was observed in the nucleotide number 815324.
Conclusion: Since the change had a heterozygous nature, it did not cause any deficiency in Frataxin protein. Given that family marriages are prevalent in Iran, there is a possibility of homozygosity with this mutation or other mutations. It is thus recommended that gene sequencing should be performed for individuals with suspected Friedrich Ataxia.
- Ataxia Friedrich, Mutation; FRDA, Iranian Patients, Homozygosity
How to Cite
References
Vicente L J, Sirena S, Pablo C. Q, Pilar G.C, Dolores M. M.The Role of Iron in Friedreich’s Ataxia: Insights From Studies in Human Tissues and Cellular and Animal Models .Frontiers in Neuroscience .2019:13.75. DOI=10.3389/fnins.2019.00075.
Gramegna LL, Tonon C, Manners DN, Pini A, Rinaldi R, Zanigni S, et al. Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich's Ataxia. Cerebellum. 2017;16(1):82-8.
Bürk K. Friedreich Ataxia: current status and future prospects. Cerebellum & Ataxias. 2017;4(1):4.
Ilg W, Bastian AJ, Boesch S, et al. Consensus paper: management of degenerative cerebellar disorders. Cerebellum. 2014;13(2):248–268. doi:10.1007/s12311-013-0531-6.
Bürk K. Friedreich Ataxia: current status and future prospects. Cerebellum Ataxias. 2017; 4:4. doi:10.1186/s40673-017-0062-x.
Ota S, Marchina E, Todeschini A, Nanetti L, Rinaldi F, Vanotti A, Mariotti C, Padovani A, Filosto M: Very Late-Onset Friedreich Ataxia with Laryngeal Dystonia. Case Rep Neurol .2014;6:287-290. doi: 10.1159/000370062.
Marmolino, D. Friedreich's ataxia: Past, present and future. Brain Research Reviews.2011: 311–330. doi: 10.1016/j.brainresrev.2011.04.001.
Entezam M, Amirfiroozi A, Togha M, Keramatipour M. Comparison of Two Different PCR-based Methods for Detection of GAA Expansions in Frataxin Gene. Iran J Public Health. 2017;46(2):222–228.
Long A, Napierala JS, Polak U, Hauser L, Koeppen AH, Lynch DR, et al. Somatic instability of the expanded GAA repeats in Friedreich’s ataxia. PLoS ONE .2017: 12(12): e0189990. doi.org/10.1371/journal.pone.0189990.
Vamshi K. Rao, Christine J. DiDonato, and Paul D. Larsen, “Friedreich’s Ataxia: Clinical Presentation of a Compound Heterozygote Child with a Rare Nonsense Mutation and Comparison with Previously Published Cases,” Case Reports in Neurological Medicine, 2018, 8587203.doi.org/10.1155/2018/8587203.
Lilian MJ, Zatz M, Kim A, Bertola D, Sugayama M, Marques-Dias M, Kok F, Ferraretto, Rosemberg S, Cocozza S, Monticelli A. Friedreichs Ataxia: Clinical and Molecular Study f 25 Brazilan Cases. Rev Hosp Clin Fac Med S Paulo 2001;56(5):143-48.
D. Potdar P, Raghu A. Molecular Diagnosis of Friedreich Ataxia Using Analysis of GAA Repeats and FXN Gene Exons in Population from Western India. Asian Journal of Neuroscience.2013, 909767.doi.org/10.1155/2013/909767.
Bürk K. Friedreich Ataxia: current status and future prospects. Cerebellum Ataxias. 2017; 4:4. doi:10.1186/s40673-017-0062-x.
Spacey S. D, Szczygielski B. I, Young S. P. Malaysian siblings with Friedreich ataxia and chorea: a novel deletion in the frataxin gene. Canadian Journal of Neurological Sciences. 2004: 31, 3, 383–386.
Ygland E., Taroni F., Gellera C., Caldarazzo S., Duno M., Soller M., Puschmann A.Atypical Friedreich ataxia in patients with FXN p.R165P point mutation or comorbid hemochromatosis . Parkinsonism and Related Disorders .2014, 20 (8), 919-923.
Charles A. Galea, Aamira Huq, Paul J. Lockhart, Geneieve Tai, Louise A. Corben, Eppie M. Yiu, Lyle C. Gurrin, David R. Lynch, Sarah Gelbard, Alexandra Durr, et al.Ann Neurol. 2016; 79(3): 485–495. doi: 10.1002/ana.24595.
Evans-Galea M. V, Corben L. A, Hasell J, et al. A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype, Neurogenetics, 2011: 12, 4, 307–313.
Sacc`a F, Marsili A, Puorro G, et al. Clinical use of frataxin measurement in a patient with a novel deletion in the FXN gene, Journal of Neurology. 2013: 260. 4, 1116–1121.
Van den Ouweland A. M. W, van Minkelen R, Bolman G. M, et al. Complete FXN deletion in a patient with FRDA. Genetic Testing and Molecular Biomarkers. 2012: 16, 1015–1018.
Gellera, C., Castellotti, B., Mariotti, C. et al. Frataxin gene point mutations in Italian Friedreich ataxia patients. Neurogenetics .2007: 8: 289. doi.org/10.1007/s10048-007-0101-5.
Doudney K, Pook M, Al-Mahdawi S, Carvajal J, Chamberlain S. A Novel Splice Site Mutation (384+1G-A) in the Friedreich's Ataxia Gene. Mutat .2007;11:415.
Pook MA, Al-Mahdawi SA, Thomas NH, Appleton R, Norman A, Mountford R, Chamberlain S.Friedreich's Ataxia: Identification of three novel frameshift mutations in patients with Friedreich’s ataxia.2000;45(2):200-6.
Potter NT, Miller CA, Anderson IJ. Mutation Detection in an Equivocal Case of Friedreich's Ataxia. Pediatr Neurol 2000;22(5):413-5.
De Castro M, Garcia-Planells J, Monros E, Canizares J, Vazquez-Manrique R, Vilchez JJ, Urtasun M, Lucas M, Navarro G, Izquierdo G, Molto MD, Palau F. Genotype and Phenotype Analysis of Friedreich's Ataxia Compound Heterozygous Patients. Hum Genet 2000;106(1):86-92.
McCormack ML, Guttmann RP, Schumann M, Farmer JM, Stolle CA, Campuzano V, Koenig M, Lynch DR. Frataxin Point Mutations in Two Patients with Friedreich's Ataxia and Unusual Clinical Features. J Neurol Neurosurg Psychiatry 2000;68(5):661-4.
Heidari MM, Khatami M, Pourakrami J. Novel Point Mutations in Frataxin Gene in Iranian Patients with Friedreich’s Ataxia. Iran J Child Neurol. 2014; 8(1):32-36.
Naseroleslami M, Parivar k, Sanjarian S, Khalili E, Aryani O, Akhavan Sepahi M, et al. Investigation of Exon 1 in FXN Gene in Patients with Clinical Symptomatic of Friedreich Ataxia. Qom Univ Med Sci J. 2012;6(4):1-7. {persian}
Naseroleslami M, Parivar K, Sanjarian S, Ariyani O, Houshmand M. Study of FRDA gene in suspect Friedrich ataxia patients. MEDICAL SCIENCES JOURNAL. 2012;21(4):275-80. {persian}
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