Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

Novel compound heterozygous mutations of ATM in ataxia-telangiectasia: A case report and calculated prevalence in the Republic of Korea

  • Jang, Min Jeong (Department of Pediatrics, Nowon Eulji Medical Center, Eulji University) ;
  • Lee, Cha Gon (Department of Pediatrics, Nowon Eulji Medical Center, Eulji University) ;
  • Kim, Hyun Jung (Department of Rehabilitation Medicine, Nowon Eulji Medical Center, Eulji University)
  • Received : 2018.08.24
  • Accepted : 2018.10.15
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Ataxia-telangiectasia (AT; OMIM 208900) is a rare autosomal recessive inherited progressive neurodegenerative disorder, with onset in early childhood. AT is caused by homozygous or compound heterozygous mutations in ATM (OMIM 607585) on chromosome 11q22. The average prevalence of the disease is estimated at 1 of 100,000 children worldwide. The prevalence of AT in the Republic of Korea is suggested to be extremely low, with only a few cases genetically confirmed thus far. Herein, we report a 5-year-old Korean boy with clinical features such as progressive gait and truncal ataxia, both ankle spasticity, dysarthria, and mild intellectual disability. The patient was identified as a compound heterozygote with two novel genetic variants: a paternally derived c.5288_5289insGA p.(Tyr1763*) nonsense variant and a maternally derived c.8363A>C p.(His2788Pro) missense variant, as revealed by next-generation sequencing and confirmed by Sanger sequencing. Based on claims data from the Health Insurance Review and Assessment Service Republic of Korea, we calculated the prevalence of AT in the Republic of Korea to be about 0.9 per million individuals, which is similar to the worldwide average. Therefore, we suggest that multi-gene panel sequencing including ATM should be considered early diagnosis.

Keywords

References

  1. Gatti R, Perlman S. Ataxia-telangiectasia. In: Adam MP, Ardinger HH, Pagon RA, eds. $GeneReviews^{(R)}$ [Internet]. Seattle: University of Washington, 1999 Mar 19 [updated 2016 Oct 27; cited 2018 Jan 6]. [https://www.ncbi.nlm.nih.gov/books/NBK26468/]
  2. Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM. Ataxia telangiectasia: a review. Orphanet J Rare Dis 2016;11:159. https://doi.org/10.1186/s13023-016-0543-7
  3. Mavrou A, Tsangaris GT, Roma E, Kolialexi A. The ATM gene and ataxia telangiectasia. Anticancer Res 2008;28:401-5.
  4. Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst) 2004;3:1187-96. https://doi.org/10.1016/j.dnarep.2004.04.010
  5. Liu XL, Wang T, Huang XJ, Zhou HY, Luan XH, Shen JY, et al. Novel ATM mutations with ataxia-telangiectasia. Neurosci Lett 2016;611:112-5. https://doi.org/10.1016/j.neulet.2015.11.036
  6. Watters DJ. Oxidative stress in ataxia telangiectasia. Redox Rep 2003;8:23-9. https://doi.org/10.1179/135100003125001206
  7. Huh HJ, Cho KH, Lee JE, Kwon MJ, Ki CS, Lee PH. Identification of ATM mutations in Korean siblings with ataxia-telangiectasia. Ann Lab Med 2013;33:217-20. https://doi.org/10.3343/alm.2013.33.3.217
  8. Jeong H, Huh HJ, Youn J, Kim JS, Cho JW, Ki CS. Ataxia-telangiectasia with novel splicing mutations in the ATM gene. Ann Lab Med 2014;34:80-4. https://doi.org/10.3343/alm.2014.34.1.80
  9. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24. https://doi.org/10.1038/gim.2015.30