DOI QR코드

DOI QR Code

The First Korean case of combined oxidative phosphorylation deficiency-17 diagnosed by clinical and molecular investigation

  • Kim, Young A (Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Kim, Yoo-Mi (Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Lee, Yun-Jin (Department of Pediatrics, Pusan National University Children's Hospital) ;
  • Cheon, Chong Kun (Department of Pediatrics, Pusan National University Children's Hospital)
  • 투고 : 2017.08.07
  • 심사 : 2017.10.23
  • 발행 : 2017.12.15

초록

Combined oxidative phosphorylation deficiency-17 (COXPD-17) is very rare and is caused by homozygous or compound heterozygous mutations in the ELAC2 gene on chromosome 17p12. The ELAC2 gene functions as a mitochondrial tRNA processing gene, and only 4 different pathogenic mutations have been reported in ELAC2-associated mitochondrial dysfunction involving oxidative phosphorylation. Affected patients show various clinical symptoms and prognosis, depending on the genotype. We report a novel mutation in the ELAC2 gene (c.95C>G [p.Pro32Arg], het), in an infant with COXPD-17 who presented with encephalopathy including central apnea and intractable epilepsy, and growth and developmental retardation. During hospitalization, consistently elevated serum lactic acid levels were noted, indicative of mitochondrial dysfunction. The patient suddenly died of shock of unknown cause at 5 months of age. This is the first case report of COXPD-17 in Korea and was diagnosed based on clinical characteristics and genetic analysis.

키워드

참고문헌

  1. De Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev 1993;15:1-22. https://doi.org/10.1016/0387-7604(93)90002-P
  2. Ojala D, Merkel C, Gelfand R, Attardi G. The tRNA genes punctuate the reading of genetic information in human mitochondrial DNA. Cell 1980;22:393-403. https://doi.org/10.1016/0092-8674(80)90350-5
  3. Montoya J, Christianson T, Levens D, Rabinowitz M, Attardi G. Identification of initiation sites for heavy-strand and light-strand transcription in human mitochondrial DNA. Proc Natl Acad Sci USA 1982;79:7195-9. https://doi.org/10.1073/pnas.79.23.7195
  4. Alvarez-Cubero MJ, Saiz M, Martinez-Gonzalez LJ, Alvarez JC, Lorente JA, Cozar JM. Genetic analysis of the principal genes related to prostate cancer: a review. Urol Oncol 2013;31:1419-29. https://doi.org/10.1016/j.urolonc.2012.07.011
  5. Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, et al. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Am J Hum Genet 2013;93:211-23. https://doi.org/10.1016/j.ajhg.2013.06.006
  6. Akawi NA, Ben-Salem S, Hertecant J, John A, Pramathan T, Kizhakkedath P, et al. A homozygous splicing mutation in ELAC2 suggests phenotypic variability including intellectual disability with minimal cardiac involvement. Orphanet J Rare Dis 2016;11:139. https://doi.org/10.1186/s13023-016-0526-8
  7. Shinwari ZMA, Almesned A, Alakhfash A, Al-Rashdan AM, Faqeih E, Al-Humaidi Z, et al. The Phenotype and outcome of infantile cardiomyopathy caused by a homozygous ELAC2 mutation. Cardiology 2017;137:188-92. https://doi.org/10.1159/000465516
  8. Tavtigian SV, Simard J, Teng DH, Abtin V, Baumgard M, Beck A, et al. A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet 2001;27:172-80. https://doi.org/10.1038/84808
  9. Ojala D, Montoya J, Attardi G. tRNA punctuation model of RNA processing in human mitochondria. Nature 1981;290:470-4. https://doi.org/10.1038/290470a0
  10. Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP. Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs. RNA Biol 2011;8:616-26. https://doi.org/10.4161/rna.8.4.15393
  11. Sanchez MI, Mercer TR, Davies SM, Shearwood AM, Nygard KK, Richman TR, et al. RNA processing in human mitochondria. Cell Cycle 2011;10:2904-16. https://doi.org/10.4161/cc.10.17.17060
  12. Tsutsui H. Oxidative stress in heart failure: the role of mitochondria. Intern Med 2001;40:1177-82. https://doi.org/10.2169/internalmedicine.40.1177
  13. Chung YW, Kang SM. An experimental approach to study the function of mitochondria in cardiomyopathy. BMB Rep 2015;48:541-8. https://doi.org/10.5483/BMBRep.2015.48.10.153

피인용 문헌

  1. Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3′‐end processing vol.40, pp.10, 2019, https://doi.org/10.1002/humu.23777
  2. Implementation of chromosomal microarrays in a cohort of patients with intellectual disability at the Argentinean public health system vol.47, pp.9, 2017, https://doi.org/10.1007/s11033-020-05743-6