Investigation of IGHMBP2 Gene Mutations Related to Charcot-Marie-Tooth in Two Khuzestanian Families by WES Method

Document Type : Original Article (s)

Authors

1 MSc, Department of Experimental Sciences, Dezful Branch, Islamic Azad University, Dezful, Iran

2 Assistant Professor, Department of Experimental Sciences, Dezful Branch, Islamic Azad University, Dezful, Iran

Abstract

Background: Charcot-Marie-Tooth disease is a group of genetically heterogeneous inherited disorders characterized by progressive sensory-motor or motor neuropathy, which often leading to leg abnormalities. The purpose of this study is to identify possible genes and mutations involved in bone genetic disorders, as well as to find new mutations that cause this disease, which can be used as background information and help to develop panels designed to diagnose this disorder.
Methods: After collecting the peripheral blood of the patients and other participants in the study, the DNA material was purified by the salting out method and sequenced with the Illumina 100X device. The standard Sanger method was used to confirm the variant.
Findings: IIn this study, two families from Khuzestan province were investigated. In the patient of the first family, NM_002180: exon3: c.449+1G>T mutation was detected, which was homozygous in the patient and heterozygous in his parents. This variant has been reported before, but it is a scarce variant that is not routinely checked. The mutation NM_002180: exon5: c.548A>C was detected in the second family.
Conclusion: By conducting more studies on a large number of families, it is possible to understand the frequency and type of mutations of genes involved in Charcot-Marie-Tooth disease in Iran and then consider the design of a special panel for this disease, which is a great help in diagnosing and preventing the disease. It will prevent the occurrence of new cases in families and improve the health of society.

Highlights

Atousa Moradzadegan: Google Scholar, PubMed

Keywords

Main Subjects

References

  1. Kazamel M, Boes CJ. Charcot Marie Tooth disease (CMT): historical perspectives and evolution. J Neurol 2015; 262(4): 801-5.
  2. Magy L, Mathis S, Le Masson G, Goizet C, Tazir M, Vallat J-M. Updating the classification of inherited neuropathies: results of an international survey. Neurology 2018; 90(10): e870-e876.
  3. Pareyson D, Saveri P, Pisciotta C. New developments in Charcot–Marie–Tooth neuropathy and related diseases. C Curr Opin Neurol 2017; 30(5): 471-80.
  4. Laurá M, Pipis M, Rossor AM, Reilly MM. Charcot–Marie–Tooth disease and related disorders: an evolving landscape. Curr Opin Neurol 2019; 32(5): 641-50.
  5. Fridman V, Bundy B, Reilly M, Pareyson D, Bacon C, Burns J, et al. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry 2015; 86(8): 873-8.
  6. Hoebeke C, Bonello-Palot N, Audic F, Boulay C, Tufod D, Attarian S, Chabrol B. Retrospective study of 75 children with peripheral inherited neuropathy: Genotype–phenotype correlations. Arch Pediatr 2018; 25(8): 452-8.
  7. Skre H. Genetic and clinical aspects of Charcot‐Marie‐Tooth's disease. Clin Genet 1974; 6(2): 98-118.
  8. Cutrupi AN, Brewer MH, Nicholson GA, Kennerson ML. Structural variations causing inherited peripheral neuropathies: A paradigm for understanding genomic organization, chromatin interactions, and gene dysregulation. Mol Genet Genomic Med 2018; 6(3): 422-33.
  9. Rzepnikowska W, Kochański A. Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscul Disord 2021; 31(12): 1266-78.
  10. Tomaselli PJ, Horga A, Rossor AM, Jaunmuktane Z, Cortese A, Blake JC, et al. IGHMBP2 mutation associated with organ-specific autonomic dysfunction. Neuromuscul Disord 2018; 28(12): 1012-5.
  11. Hoyle JC, Isfort MC, Roggenbuck J, Arnold WD. The genetics of Charcot–Marie–Tooth disease: current trends and future implications for diagnosis and management. Appl Clin Genet 2015; 8: 235-43.
  12. Dohrn MF, Glöckle N, Mulahasanovic L, Heller C, Mohr J, Bauer C, et al. Frequent genes in rare diseases: panel‐based next generation sequencing to disclose causal mutations in hereditary neuropathies. J Neurochem 2017; 143(5): 507-22.
  13. Satam H, Joshi K, Mangrolia U, Waghoo S, Zaidi G, Rawool S, et al. Next-generation sequencing technology: current trends and advancements. Biology (Basel) 2023; 12(7): 997.
  14. Azevedo H, Pupe C, Pereira R, Nascimento OJ. Pain in Charcot-Marie-Tooth disease: an update. Arq Neuropsiquiatr 2018; 76(4): 273-6.
  15. Kwon HM, Choi B-O. Analyzing clinical and genetic aspects of axonal Charcot-Marie-Tooth disease. Journal of Genetic Medicine 2021; 18(2): 83-93.
  16. Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, et al. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet 2014; 95(5): 590-601.
  17. Tian Y, Xing J, Shi Y, Yuan E. Exploring the relationship between IGHMBP2 gene mutations and spinal muscular atrophy with respiratory distress type 1 and Charcot-Marie-Tooth disease type 2S: A systematic review. Front Neurosci 2023; 17: 1252075.
  18. Gentile L, Russo M, Taioli F, Ferrarini M, Aguennouz MH, Rodolico C, et al. Rare among rare: phenotypes of uncommon CMT genotypes. Brain Sci 2021; 11(12): 1616.
  19. Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yau WY, et al. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 2019; 51(4): 649-58.
Journal of Isfahan Medical School
Volume 42, Issue 782
2nd Week, November
November and December 2024
Pages 783-790

Files

History

  • Receive Date: 05 September 2024
  • Revise Date: 08 December 2024
  • Accept Date: 08 December 2024

Share

How to cite

Statistics