The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: Autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

被引：35

作者：

Lai J.-P. ^{[1
]}

Liu Y.-C. ^{[1
]}

Alimchandani M. ^{[1
]}

Liu Q. ^{[1
]}

Aung P.P. ^{[1
]}

Matsuda K. ^{[1
]}

Lee C.-C.R. ^{[1
]}

Tsokos M. ^{[1
]}

Hewitt S. ^{[1
]}

Rushing E.J. ^{[2
]}

Tamura D. ^{[3
]}

Levens D.L. ^{[1
]}

DiGiovanna J.J. ^{[3
]}

Fine H.A. ^{[4
]}

Patronas N. ^{[5
]}

Khan S.G. ^{[3
]}

Kleiner D.E. ^{[1
]}

Oberholtzer J.C. ^{[1
]}

Quezado M.M. ^{[1
]}

Kraemer K.H. ^{[3
]}

机构：

[1] Center for Cancer Research, National Cancer Institute, National Institutes of Health, Laboratory of Pathology, Bethesda, 20892, MD

[2] University of Zurich, Institute of Neuropathology, Zurich

[3] Center for Cancer Research, National Cancer Institute, National Institutes of Health, DNA Repair Section, Dermatology Branch, Bethesda, 20892, MD

[4] National Cancer Institute, National Institutes of Health, Neuro-Oncology Branch, Center for Cancer Research, Bethesda, 20892, MD

[5] Clinical Center National Institutes of Health, Radiology and Imaging Sciences, Bethesda, 20892, MD

来源：

Acta Neuropathologica Communications | / 1卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Cachexia; DNA damage; DNA repair; Glioblastoma; Neurodegeneration;

D O I：

10.1186/2051-5960-1-4

中图分类号：

学科分类号：

摘要：

Background: To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D. Results: The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient. Conclusions: These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients. © 2013 Lai et al.; licensee BioMed Central Ltd.

引用

共 61 条

[1] Bradford P.T., Goldstein A.M., Tamura D., Khan S.G., Ueda T., Boyle J., Oh K.S., Imoto K., Inui H., Moriwaki S., Emmert S., Pike K.M., Raziuddin A., Plona T.M., DiGiovanna J.J., Tucker M.A., Kraemer K.H., Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair, J Med Genet, 48, pp. 168-176, (2011)
[2] Kraemer K.H., Lee M.M., Andrews A.D., Lambert W.C., The role of sunlight and DNA repair in melanoma and nonmelanoma skin cancer. The xeroderma pigmentosum paradigm, Arch Dermatol, 130, pp. 1018-1021, (1994)
[3] Kraemer K.H., Lee M.M., Scotto J., Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases, Arch Dermatol, 123, pp. 241-250, (1987)
[4] Robbins J.H., Kraemer K.H., Lutzner M.A., Festoff B.W., Coon H.G., Xeroderma pigmentosum. An inherited disease with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair, Ann Intern Med, 80, pp. 221-248, (1974)
[5] Anttinen A., Koulu L., Nikoskelainen E., Portin R., Kurki T., Erkinjuntti M., Jaspers N.G., Raams A., Green M.H., Lehmann A.R., Wing J.F., Arlett C.F., Marttila R.J., Neurological symptoms and natural course of xeroderma pigmentosum, Brain, 131, pp. 1979-1989, (2008)
[6] Itoh M., Hayashi M., Shioda K., Minagawa M., Isa F., Tamagawa K., Morimatsu Y., Oda M., Neurodegeneration in hereditary nucleotide repair disorders, Brain Dev, 21, pp. 326-333, (1999)
[7] Kanda T., Oda M., Yonezawa M., Tamagawa K., Isa F., Hanakago R., Tsukagoshi H., Peripheral neuropathy in xeroderma pigmentosum, Brain, 113, pp. 1025-1044, (1990)
[8] Robbins J.H., Xeroderma pigmentosum. Defective DNA repair causes skin cancer and neurodegeneration, JAMA, 260, pp. 384-388, (1988)
[9] Robbins J.H., Brumback R.A., Mendiones M., Barrett S.F., Carl J.R., Cho S., Denckla M.B., Ganges M.B., Gerber L.H., Guthrie R.A., Neurological disease in xeroderma pigmentosum, Documentation of a late onset type of the juvenile onset form. Brain, 114, pp. 1335-1361, (1991)
[10] Robbins J.H., Kraemer K.H., Merchant S.N., Brumback R.A., Adult-onset xeroderma pigmentosum neurological disease-observations in an autopsy case, Clin Neuropathol, 21, pp. 18-23, (2002)

← 1 2 3 4 5 6 7 →