Journal of Genetic Medicine

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

DOI QR Code

Xeroderma pigmentosum group A with mutational hot spot (c.390-1G>C in XPA ) in South Korea

  • Choi, Jung Yoon (Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University) ;
  • Yun, Hyung Ho (Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University) ;
  • Lee, Cha Gon (Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University)
  • Received : 2016.03.25
  • Accepted : 2016.05.30
  • Published : 2016.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Xeroderma pigmentosum (XP) is rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. We reported the first molecularly confirmed Korean patient of XP by targeted exome sequencing. The prevalence of XP included all subtype and carrier frequency of XP-A the using public data were estimated for the first time in South Korea. Materials and Methods: We described a 4-year-old Korean girl with clinical diagnosis of XP. We performed targeted exome sequencing in the patient for genetic confirmation considering disease genetic heterogeneity and for differential diagnosis. We verified a carrier frequency of c.390-1G>C in XPA gene known as mutational hot spot using Korean Reference Genome Data Base. We estimated the period prevalence of all subtypes of XP based on claims data of the Health Insurance Review and Assessment Service in South Korea. Results: We identified homozygous splicing mutation of XPA (c.390-1G>C) in the patient. The carrier frequency of risk for XPA (c.390-1G>C) was relatively high 1.608 e-03 (allele count 2/1244). The prevalence of XP in South Korea was 0.3 per million people. Conclusion: We expect that c.390-1G>C is hot spot for the mutation of XPA and possible founder variant in South Korea. However, the prevalence in South Korea was extremely low compared with Western countries and Japan.

Keywords

References

  1. Cleaver JE. Defective repair replication of DNA in xeroderma pigmentosum. Nature 1968;218:652-6. https://doi.org/10.1038/218652a0
  2. Spivak G, Hanawalt PC. Photosensitive human syndromes. Mutat Res 2015;776:24-30. https://doi.org/10.1016/j.mrfmmm.2014.11.003
  3. Moriwaki S. Human DNA repair disorders in dermatology: a historical perspective, current concepts and new insight. J Dermatol Sci 2016;81:77-84. https://doi.org/10.1016/j.jdermsci.2015.09.008
  4. Feltes BC, Bonatto D. Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications. Mutat Res Rev Mutat Res 2015;763:306-20. https://doi.org/10.1016/j.mrrev.2014.12.002
  5. Lehmann AR. Xeroderma pigmentosum in the United Kingdom. Photochem Photobiol 2015;91:484-5. https://doi.org/10.1111/php.12301
  6. Kraemer KH, DiGiovanna JJ. Forty years of research on xeroderma pigmentosum at the US National Institutes of Health. Photochem Photobiol 2015;91:452-9. https://doi.org/10.1111/php.12345
  7. Ueda T, Kanda F, Aoyama N, Fujii M, Nishigori C, Toda T. Neuroimaging features of xeroderma pigmentosum group A. Brain Behav 2012;2:1-5. https://doi.org/10.1002/brb3.22
  8. Tanioka M, Budiyant A, Ueda T, Nagano T, Ichihashi M, Miyachi Y, et al. A novel XPA gene mutation and its functional analysis in a Japanese patient with xeroderma pigmentosum group A. J Invest Dermatol 2005;125:244-6. https://doi.org/10.1111/j.0022-202X.2005.23783.x
  9. Health Insurance Review & Assessment Service (HIRA). HIRA-PPS [Internet]. Wonju, Korea: HIRA, 2015 [cited 2016 Jun 1]. [http://opendata.hira.or.kr/op/opc/selectPatDataAplInfoView.do]
  10. Korea National Research Institute of Health. Korean Referenece Genome 2016 [Internet]. Cheongju, Korea: Korea National Research Institute of Health, 2016 [cited 2016 Jan 1]. [http://152.99.75.168/KRGDB/browser/mainBrowser.jsp]
  11. Kraemer KH, DiGiovanna JJ. Xeroderma Pigmentosum. 2003 Jun 20 [updated 2014 Feb 13]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al, editors. $GeneReviews^{(R)}$ [Internet]. Seattle (WA): University of Washington, 1993-2016 [cited 2016 Jun 1]. [http://www.ncbi.nlm.nih.gov/books/NBK1397/]
  12. Sidwell RU, Sandison A, Wing J, Fawcett HD, Seet JE, Fisher C, et al. A novel mutation in the XPA gene associated with unusually mild clinical features in a patient who developed a spindle cell melanoma. Br J Dermatol 2006;155:81-8. https://doi.org/10.1111/j.1365-2133.2006.07272.x
  13. Kleijer WJ, Laugel V, Berneburg M, Nardo T, Fawcett H, Gratchev A, et al. Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. DNA Repair (Amst) 2008;7:744-50. https://doi.org/10.1016/j.dnarep.2008.01.014
  14. Kraemer KH, Slor H. Xeroderma pigmentosum. Clin Dermatol 1985;3:33-69. https://doi.org/10.1016/0738-081X(85)90096-3
  15. Imoto K, Nadem C, Moriwaki S, Nishigori C, Oh KS, Khan SG, et al. Ancient origin of a Japanese xeroderma pigmentosum founder mutation. J Dermatol Sci 2013;69:175-6. https://doi.org/10.1016/j.jdermsci.2012.10.008
  16. Cleaver JE. Common pathways for ultraviolet skin carcinogenesis in the repair and replication defective groups of xeroderma pigmentosum. J Dermatol Sci 2000;23:1-11. https://doi.org/10.1016/S0923-1811(99)00088-2
  17. Hirai Y, Kodama Y, Moriwaki S, Noda A, Cullings HM, Macphee DG, et al. Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene comprise nearly 1% of the Japanese population. Mutat Res 2006;601:171-8.
  18. Nishigori C, Moriwaki S, Takebe H, Tanaka T, Imamura S. Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan. Arch Dermatol 1994;130:191-7. https://doi.org/10.1001/archderm.1994.01690020057009