Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
권호 표지
DOI QR코드

DOI QR Code

Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia

  • Bae, Kunho (Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Song, Ju Sun (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Chung (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Nayoung K.D. (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Woong-Yang (Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Byoung Joon (Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ki, Chang-Seok (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Sang Jin (Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2016.12.15
  • Accepted : 2017.05.31
  • Published : 2017.09.01
⟨ Previous Next ⟩

Abstract

Choroideremia is a rare X-linked disorder causing progressive chorioretinal atrophy. Affected patients develop night blindness with progressive peripheral vision loss and eventual blindness. Herein, we report two Korean families with choroideremia. Multimodal imaging studies showed that the probands had progressive loss of visual field with characteristic chorioretinal atrophy, while electroretinography demonstrated nearly extinguished cone and rod responses compatible with choroideremia. Sanger sequencing of all coding exons and flanking intronic regions of the CHM gene revealed a novel small deletion at a splice site (c.184_189+3delTACCAGGTA) in one patient and a deletion of the entire exon 9 in the other. This is the first report on a molecular genetic diagnosis of choroideremia in Korean individuals. Molecular diagnosis of choroideremia should be widely adopted for proper diagnosis and the development of new treatment modalities including gene therapy.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfare, National Research Foundation of Korea (NRF)

References

  1. Rafuse EV and McCulloch C. Choroideremia. A pathological report. Can J Ophthalmol 1968;3:347-52.
  2. Rubin ML, Fishman RS, McKay RA. Choroideremia. Study of a family and literature review. Arch Ophthalmol 1966;76:563-74. https://doi.org/10.1001/archopht.1966.03850010565015
  3. MacDonald IM, Hume S, Chan S, Seabra MC. Choroideremia. In: Pragon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al. eds. GeneReviews [Internet], Seattle, WA: University of Washington, 1993-2015.
  4. Roberts MF, Fishman GA, Roberts DK, Heckenlively JR, Weleber RG, Anderson RJ, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia. Br J Ophthalmol 2002; 86:658-62. https://doi.org/10.1136/bjo.86.6.658
  5. MacDonald IM, Chen MH, Addison DJ, Mielke BW, Nesslinger NJ. Histopathology of the retinal pigment epithelium of a female carrier of choroideremia. Can J Ophthalmol 1997;32:329-33.
  6. Seabra MC, Brown MS, Slaughter CA, Sudhof TC, Goldstein JL. Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product. Cell 1992;70:1049-57. https://doi.org/10.1016/0092-8674(92)90253-9
  7. van den Hurk JA, Schwartz M, van Bokhoven H, van de Pol TJ, Bogerd L, Pinckers AJ, et al. Molecular basis of choroideremia (CHM): mutations involving the Rab escort protein-1 (REP-1) gene. Hum Mutat 1997;9: 110-7. https://doi.org/10.1002/(SICI)1098-1004(1997)9:2<110::AID-HUMU2>3.0.CO;2-D
  8. Pfeffer SR. Rab GTPases: master regulators of membrane trafficking. Curr Opin Cell Biol 1994;6:522-6. https://doi.org/10.1016/0955-0674(94)90071-X
  9. Sanchez-Alcudia R, Garcia-Hoyos M, Lopez-Martinez MA, Sanchez-Bolivar N, Zurita O, Gimenez A, et al. A comprehensive analysis of choroideremia: From genetic characterization to clinical practice. PLoS One 2016;11:e0151943. https://doi.org/10.1371/journal.pone.0151943
  10. Sergeev YV, Smaoui N, Sui R, Stiles D, Gordiyenko N, Strunnikova N, et al. The functional effect of pathogenic mutations in Rab escort protein 1. Mutat Res 2009;665:44-50. https://doi.org/10.1016/j.mrfmmm.2009.02.015
  11. O SJ, Kim SH, Lee HY. A case of choroideremia with recurrent anterior uveitis. Korean J Ophthalmol 2003;17:55-62. https://doi.org/10.3341/kjo.2003.17.1.55
  12. Lee CY and Shin TY. Choroideremia. J Korean Ophthalmol Soc 1981; 22:433-8.
  13. Korea National Research Institute of Health. Korean Reference Genome Database (KRGDB). http://152.99.75.168/KRGDB (Accessed on May 2016).
  14. Exome Aggregation Consortium (ExAC). http://exac.broadinstitute.org (Accessed on May 2016).
  15. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. 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
  16. Ramsden SC, O'Grady A, Fletcher T, O'Sullivan J, Hart-Holden N, Barton SJ, et al. A clinical molecular genetic service for United Kingdom families with choroideraemia. Eur J Med Genet 2013;56:432-8. https://doi.org/10.1016/j.ejmg.2013.06.003
  17. Shimizu K, Oishi A, Oishi M, Ogino K, Morooka S, Sugahara M, et al. Next-Generation Sequencing-based molecular diagnosis of choroideremia. Case Rep Ophthalmol 2015;6:246-50. https://doi.org/10.1159/000437348
  18. Li S, Guan L, Fang S, Jiang H, Xiao X, Yang J, et al. Exome sequencing reveals CHM mutations in six families with atypical choroideremia initially diagnosed as retinitis pigmentosa. Int J Mol Med 2014;34:573-7. https://doi.org/10.3892/ijmm.2014.1797
  19. Furgoch MJ, Mewes-Ares J, Radziwon A, Macdonald IM. Molecular genetic diagnostic techniques in choroideremia. Mol Vis 2014;20:535-44.

Cited by

  1. Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa vol.37, pp.3, 2017, https://doi.org/10.3346/jkms.2022.37.e5