Abstract
Progressive neurological symptoms, including hearing loss, occur in some patients with xeroderma pigmentosum (XP). Patients with neurodegeneration commonly have mutations in XP-A, XP-B, XP-D, XP-F, or XP-G. Typically, audiograms of patients with XP who have sensorineural hearing loss are downsloping. The degree of hearing loss is directly correlated with neurological involvement, including cognitive impairment. Thus, for audiometric assessment, auditory brainstem response (ABR) or other objective tests are sometimes required instead of pure-tone audiometry. In the human temporal bone, XP-mediated pathology includes atrophy of the organ of Corti, stria vascularis, and spiral ganglion neurons. Xpa-deficient mice also showed significant loss of spiral ganglion neurons in the cochlea. Several studies show that the cochlea and nervous system in patients with XP are susceptible to persistent genomic stress, such as reactive oxygen species (ROS), which leads to early onset of sensorineural hearing loss. Regular audiometric monitoring of the hearing status of patients with XP to identify the need for auditory interventions, such as hearing aids, is important for maintaining their quality of life.
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References
Bradford PT, Goldstein AM, Tamura D, et al. Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair. J Med Genet. 2011;48:168–76.
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.
Anttinen A, Koulu L, Nikoskelainen E, et al. Neurological symptoms and natural course of xeroderma pigmentosum. Brain. 2008;131(8):1979–89.
Totonchy MB, Tamura D, Pantell MS, et al. Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration. Brain. 2013;136:194–208.
Longridge NS. Audiological assessment of deafness associated with xeroderma pigmentosa. J Laryngol Otol. 1976;90:539–51.
Kenyon GS, Booth JB, Prasher DK, et al. Neuro-otological abnormalities in xeroderma pigmentosum with particular reference to deafness. Brain. 1985;108:771–84.
Nishigori C, Moriwaki S, Takebe H, et al. Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan. Arch Dermatol. 1994;130:191–7.
Hirai Y, Kodama Y, Moriwaki S, 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.
Robbins JH, Kraemer KH, Lutzner MA, et al. Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med. 1974;80:221–48.
Moriwaki S, Kraemer KH. Xeroderma pigmentosum – bridging a gap between clinic and laboratory. Photodermatol Photoimmunol Photomed. 2001;17:47–54.
DiGiovanna JJ, Kraemer KH. Shining a light on xeroderma pigmentosum. J Invest Dermatol. 2012;132:785–96.
Ueda T, Kanda F, Aoyama N, Fujii M, Nishigori C, Toda T. Neuroimaging features of xeroderma pigmentosum group A. Brain Behav. 2012;2(1):1–5.
Wong AC, Ryan AF. Mechanisms of sensorineural cell damage, death and survival in the cochlea. Front Aging Neurosci. 2015;7:58.
Viana LM, Seyyedi M, Brewer CC, et al. Histopathology of the inner ear in patients with xeroderma pigmentosum and neurologic degeneration. Otol Neurotol. 2013;34:1230–6.
Robbins JH, Kraemer KH, Merchant SN, et al. Adult-onset xeroderma pigmentosum neurological disease – observations in an autopsy case. Clin Neuropathol. 2002;21:18–23.
Shinomiya H, Yamashita D, Fujita T, et al. Hearing dysfunction in Xpa-deficient mice. Front Aging Neurosci. 2017;10(9):19.
Nakane H, Takeuchi S, Yuba S, et al. High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene. Nature. 1995;377:165–8.
Fousteri M, Mullenders LH. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 2008;18:73–84.
Guthrie OW, Li-Korotky HS, Durrant JD, Balaban C. Cisplatin induces cytoplasmic to nuclear translocation of nucleotide excision repair factors among spiral ganglion neurons. Hear Res. 2008;239(1–2):79–91.
Guthrie OW, Carrero-Martínez FA. Real-time quantification of Xeroderma pigmentosum mRNA from the mammalian cochlea. Ear Hear. 2010;31(5):714–21.
Staecker H, Zheng QY, Van De Water H, et al. Oxidative stress in aging in the C57B16/J mouse cochlea. Acta Otolaryngol. 2001;121:666–72.
Brooks PJ. The 8,5′-cyclopurine-2′-deoxynucleosides: candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair. DNA Repair. 2008;7:1168–79.
Morris DP, Alian W, Maessen H, et al. Cochlear implantation in Cockayne syndrome: our experience of two cases with different outcomes. Laryngoscope. 2007;117(5):939–43.
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Fujita, T., Yamashita, D. (2019). Hearing Impairment in Xeroderma Pigmentosum: Animal Models and Human Studies. In: Nishigori, C., Sugasawa, K. (eds) DNA Repair Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-10-6722-8_4
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DOI: https://doi.org/10.1007/978-981-10-6722-8_4
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