Epidemiological Study of Xeroderma Pigmentosum in Japan: Genotype-Phenotype Relationship

  • Chikako NishigoriEmail author
  • Eiji Nakano


Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by the deficiency of repairing DNA damage caused by ultraviolet radiation and some other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun-exposed body sites, and some patients show exaggerated severe sunburn upon minimum sun exposure and neurological symptoms. We have conducted the nationwide survey for XP since 1980 as a research project supported for the intractable disease initiated by the Japanese Ministry of Health, Labour and Welfare. The frequency of each complementation group in Japan is considerably different from that in Western countries; in Japan, XP complementation group A is the most frequent, followed by variant type. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that patients with XP developed, followed by squamous cell carcinoma and malignant melanoma. The frequency of these skin cancers in patients with XP-A has decreased in these 20 years, and ages of onset of developing skin cancers are much older than those previously observed, which is greatly attributed to the education of sun protection for the patients with XP and their parents and guardians for these 20 years. In order to encourage the patients and their parents to perform appropriate sun protection for the prevention from skin cancers, definite diagnosis but not possible diagnosis is crucial. In addition, diagnosing at younger ages is important. On the other hand, the effective therapy for neurologic XP has not been established yet, and this needs to be done urgently.



Most of the work in this chapter was supported by the Ministry of Health, Labour and Welfare, which is a research on intractable diseases. The authors appreciate patients’ cooperation.


  1. 1.
    Takebe H, Nishigori C, Satoh Y. Genetics and skin cancer of xeroderma pigmentosum in Japan. Jpn J Cancer Res. 1987;78(11):1135–43.PubMedGoogle Scholar
  2. 2.
    Hirai Y, Kodama Y, Moriwaki S, et al. Heterozygous individuals bearing a non-functional allele at XPA gene exist in nearly 1% of Japanese populations. Mutat Res. 2006;601(1–2):171–8.CrossRefGoogle Scholar
  3. 3.
    Sato Y, Nishigori C. Xeroderma pigmentosum: clinical aspects. Gann Monogr Cancer Res. 1988;35:113–26.Google Scholar
  4. 4.
    Nakano E, Ono R, Masaki T, et al. Differences in clinical phenotype among patients with XP complementation group D: 3D structure and ATP-docking of XPD in silico. J Investig Dermatol. 2014;134(6):1775–8.CrossRefGoogle Scholar
  5. 5.
    Nakano E, Masaki T, Kanda F, et al. The present status of xeroderma pigmentosum in Japan and a tentative severity classification scale. Exp Dermatol. 2016;25(Suppl 3):28–33.CrossRefGoogle Scholar
  6. 6.
    Ono R, Masaki T, Takeuchi S, et al. Three school-age cases of xeroderma pigmentosum variant type. Photodermatol Photoimmunol Photomed. 2013;29(3):132–9.CrossRefGoogle Scholar
  7. 7.
    Hayashi M. Treatment, rehabilitation, and home care of xeroderma pigmentosum (XP); intractable disease and home care [in Japanese]. Home Health Care for the People with Intractable Diseases. 2008;14(9):58–61.Google Scholar
  8. 8.
    Hiroshima K, Inoue S. Symptoms of locomotorium in patients with xeroderma pigmentosum and the treatment; for maintenance of QOL [in Japanese]. J Clin Exp Med. 2009;228(2):147–53.Google Scholar
  9. 9.
    Nishigori C, Moriwaki S, Takebe H, et al. Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan. Arch Dermatol. 1994;130(2):191–7.CrossRefGoogle Scholar
  10. 10.
    Kanda T, Oda M, Yonezawa M, et al. Peripheral neuropathy in xeroderma pigmentosum. Brain. 1990;113(Pt4):1025–44.CrossRefGoogle Scholar
  11. 11.
    Ueda T, Kanda F, Aoyama N, et al. Neuroimaging features of xeroderma pigmentosum group A. Brain Behav. 2012;2(1):1–5.CrossRefGoogle Scholar
  12. 12.
    Moriwaki S, Nishigori C, Imamura S, et al. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Dermatol. 1993;128(1):91–4.CrossRefGoogle Scholar
  13. 13.
    Mimaki T, Tanaka K, Nagai A, et al. Neurological symptoms of group A of xeroderma pigmentosum and molecular genetic study [in Japanese]. Jpn J Clin Med. 1993;51(9):2488–93.Google Scholar
  14. 14.
    Imoto K, Nadem C, Moriwaki S, et al. Ancient origin of a Japanese xeroderma pigmentosum founder mutation. J Dermatol Sci. 2015;69(2):175–6.CrossRefGoogle Scholar
  15. 15.
    Satokata I, Tanaka K, Miura N, et al. Characterization of a splicing mutation in group A xeroderma pigmentosum. Proc Natl Acad Sci U S A. 1990;87(24):9908–12.CrossRefGoogle Scholar
  16. 16.
    Sato K, Watatani M, Ikenaga M, et al. Sensitivity to UV radiation of fibroblasts from a Japanese group A xeroderma pigmentosum patient with mild neurological abnormalities. Br J Dermatol. 1987;116(1):101–8.CrossRefGoogle Scholar
  17. 17.
    Kondoh M, Ueda M, Nakagawa K, et al. Siblings with xeroderma pigmentosum complementation group A with different skin cancer development: importance of sun protection at an early age. J Am Acad Dermatol. 1994;31(6):993–6.CrossRefGoogle Scholar
  18. 18.
    Sato M, Nishigori C, Yagi T, et al. Aberrant splicing and truncated-protein expression due to a newly identified XPA gene mutation. Mutat Res. 1996;362(2):199–208.CrossRefGoogle Scholar
  19. 19.
    Takahashi Y, Endo Y, Sugiyama Y, et al. XPA gene mutations resulting in subtle truncation of protein in xeroderma pigmentosum group A patients with mild skin symptoms. J Investig Dermatol. 2010;130(10):2481–8.CrossRefGoogle Scholar
  20. 20.
    Takeuchi S, Nakano E, Yamashita D, et al. A mild case of xeroderma pigmentosum type A. J Pediatr Dermatol. 2013;32(2):167–72.Google Scholar
  21. 21.
    Masaki T, Tsujimoto M, Kitazawa R, Funasaka Y, Ichihashi M, Kitazawa S, Kakita A, Kanda F, Nishigori C. Autopsy findings and clinical features of mild type xeroderma pigmentosum complementation group A. Siblings: 40 years follow up. J Am Acad Dermatol.Google Scholar
  22. 22.
    Nishigori C, Zghal M, Yagi T, et al. High prevalence of the point mutation in exon 6 of the xeroderma pigmentosum group A-complementing (XPAC) gene in xeroderma pigmentosum group A patients in Tunisia. Am J Hum Genet. 1993;53(5):1001–6.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Sidwell RU, Sandison A, Wing J, 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(1):81–8.CrossRefGoogle Scholar
  24. 24.
    Takahashi Y, Endo Y, Kusaka-Kikushima A, et al. An XPA gene splicing mutation resulting in trace protein expression in an elderly patient with xeroderma pigmentosum group A without neurological abnormalities. Br J Dermatol. 2016;177(1):253–7. Scholar
  25. 25.
    Ono R, Masaki T, Pozo FM, et al. TA 10-year follow-up of a child with mild cases of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing. Photodermatol Photoimmunol Photomed. 2016;32(4):174–80.CrossRefGoogle Scholar
  26. 26.
    Nakano E, Takeuchi S, Ono R, Tsujimoto M, Masaki T, Nishigori C. Xeroderma pigmentosum diagnosis using a flow cytometry-based nucleotide excise on repair assay. J Investig Dermatol. 2018;138(2):467–70.CrossRefGoogle Scholar
  27. 27.
    Tanioka M, Masaki T, Ono R, et al. Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type. J Investig Dermatol. 2007;127(7):1745–51.CrossRefGoogle Scholar
  28. 28.
    Nagore E, Sevila A, Sanmartin O, et al. Excellent response of basal cell carcinoma and pigmentary changes in xeroderma pigmentosum to imiquimod 5% cream. Br J Dermatol. 2003;149:858–61.CrossRefGoogle Scholar
  29. 29.
    Saffi J, Agnoletto MH, Guecheva TN, et al. Effect of the anti-neoplastic drug doxorubicin on XPD-mutated DNA repair-deficient human cells. DNA Repair (Amst). 2010;9(1):40–7.CrossRefGoogle Scholar
  30. 30.
    Sumiyoshi M, Soda H, Sadanaga N, et al. Alert regarding Cisplatin-induced severe adverse events in cancer patients with xeroderma pigmentosum. Intern Med. 2017;56(8):979–82.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Dermatology, Graduate School of MedicineKobe UniversityKobeJapan

Personalised recommendations