DNA repair-deficiency disorder

A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

DNA repair defects can cause an accelerated aging disease or an increased risk of cancer, or sometimes both.

## Contents

* 1 DNA repair defects and accelerated aging
* 1.1 Human disorders with accelerated aging
* 1.2 Examples
* 1.3 DNA repair defects distinguished from "accelerated aging"
* 1.4 Debate concerning "accelerated aging"
* 2 DNA repair defects and increased cancer risk
* 3 See also
* 4 References
* 5 External links

## DNA repair defects and accelerated aging

DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.[citation needed]

### Human disorders with accelerated aging

* Ataxia-telangiectasia
* Bloom syndrome
* Cockayne syndrome
* Fanconi anemia
* Progeria (Hutchinson–Gilford progeria syndrome)
* Rothmund–Thomson syndrome
* Trichothiodystrophy
* Werner syndrome
* Xeroderma pigmentosum

### Examples

Some examples of DNA repair defects causing progeroid syndromes in humans or mice are shown in Table 1.

Table 1. DNA repair proteins that, when deficient, cause features of accelerated aging (segmental progeria).  Protein | Pathway | Description

|
|

ATR | Nucleotide excision repair[1] | deletion of ATR in adult mice leads to a number of disorders including hair loss and graying, kyphosis, osteoporosis, premature involution of the thymus, fibrosis of the heart and kidney and decreased spermatogenesis[2]
DNA-PKcs | Non-homologous end joining | shorter lifespan, earlier onset of aging related pathologies;[3][4] higher level of DNA damage persistence[5]
ERCC1
ERCC2 (XPD)  | Nucleotide excision repair (also transcription as part of TFIIH)  | some mutations in ERCC2 cause Cockayne syndrome in which patients have segmental progeria with reduced stature, intellectual disability, cachexia (loss of subcutaneous fat tissue), sensorineural deafness, retinal degeneration, and calcification of the central nervous system; other mutations in ERCC2 cause trichothiodystrophy in which patients have segmental progeria with brittle hair, short stature, progressive cognitive impairment and abnormal face shape; still other mutations in ERCC2 cause xeroderma pigmentosum (without a progeroid syndrome) and with extreme sun-mediated skin cancer predisposition[6]
ERCC4 (XPF)  | Nucleotide excision repair, Interstrand cross link repair, Single-strand annealing, Microhomology-mediated end joining[7] | mutations in ERCC4 cause symptoms of accelerated aging that affect the neurologic, hepatobiliary, musculoskeletal, and hematopoietic systems, and cause an old, wizened appearance, loss of subcutaneous fat, liver dysfunction, vision and hearing loss, chronic kidney disease, muscle wasting, osteopenia, kyphosis and cerebral atrophy[7]
ERCC5 (XPG)  | Nucleotide excision repair,[8] Homologous recombinational repair,[9] Base excision repair[10][11] | mice with deficient ERCC5 show loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months
ERCC6 (Cockayne syndrome B or CS-B)  | Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]  | premature aging features with shorter life span and photosensitivity,[12] deficient transcription coupled NER with accumulation of unrepaired DNA damages,[13] also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines[13]
ERCC8 (Cockayne syndrome A or CS-A)  | Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]  | premature aging features with shorter life span and photosensitivity,[12] deficient transcription coupled NER with accumulation of unrepaired DNA damages,[13] also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines[13]
GTF2H5 (TTDA)  | Nucleotide excision repair | deficiency causes trichothiodystrophy (TTD) a premature-ageing and neuroectodermal disease; humans with GTF2H5 mutations have a partially inactivated protein[14] with retarded repair of 6-4-photoproducts[15]
Ku70  | Non-homologous end joining | shorter lifespan, earlier onset of aging related pathologies;[16] persistent foci of DNA double-strand break repair proteins[17]
Ku80  | Non-homologous end joining | shorter lifespan, earlier onset of aging related pathologies;[18] defective repair of spontaneous DNA damage[16]
Lamin A | Non-homologous end joining, Homologous recombination | increased DNA damage and chromosome aberrations; progeria; aspects of premature aging; altered expression of numerous DNA repair factors[19]
NRMT1  | Nucleotide excision repair[20] | mutation in NRMT1 causes decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration[21]
RECQL4 | Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining[22] | mutations in RECQL4 cause Rothmund-Thomson syndrome, with alopecia, sparse eyebrows and lashes, cataracts and osteoporosis[22]
SIRT6  | Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining [23] | SIRT6-deficient mice develop profound lymphopenia, loss of subcutaneous fat and lordokyphosis, and these defects overlap with aging-associated degenerative processes[24]
SIRT7  | Non-homologous end joining | mice defective in SIRT7 show phenotypic and molecular signs of accelerated aging such as premature pronounced curvature of the spine, reduced life span, and reduced non-homologous end joining[25]
Werner syndrome helicase | shorter lifespan, earlier onset of aging related pathologies, genome instability[26][27]
ZMPSTE24  | Homologous recombination | lack of Zmpste24 prevents lamin A formation and causes progeroid phenotypes in mice and humans, increased DNA damage and chromosome aberrations, sensitivity to DNA-damaging agents and deficiency in homologous recombination[28]

### DNA repair defects distinguished from "accelerated aging"

Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (often some of both).[29] But elimination of any gene essential for base excision repair kills the embryo—it is too lethal to display symptoms (much less symptoms of cancer or "accelerated aging").[30] Rothmund-Thomson syndrome and xeroderma pigmentosum display symptoms dominated by vulnerability to cancer, whereas progeria and Werner syndrome show the most features of "accelerated aging". Hereditary nonpolyposis colorectal cancer (HNPCC) is very often caused by a defective MSH2 gene leading to defective mismatch repair, but displays no symptoms of "accelerated aging".[31] On the other hand, Cockayne Syndrome and trichothiodystrophy show mainly features of accelerated aging, but apparently without an increased risk of cancer[32] Some DNA repair defects manifest as neurodegeneration rather than as cancer or "accelerated aging".[33] (Also see the "DNA damage theory of aging" for a discussion of the evidence that DNA damage is the primary underlying cause of aging.)

### Debate concerning "accelerated aging"

Some biogerontologists question that such a thing as "accelerated aging" actually exists, at least partly on the grounds that all of the so-called accelerated aging diseases are segmental progerias. Many disease conditions such as diabetes, high blood pressure, etc., are associated with increased mortality. Without reliable biomarkers of aging it is hard to support the claim that a disease condition represents more than accelerated mortality.[34]

Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage.[29] The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging".[35] Such conditions, it is argued, are readily distinguishable from genetic diseases associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis and sickle cell anemia. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases such as cancer and Alzheimer's disease.[36]

## DNA repair defects and increased cancer risk

Individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer.[37] When a mutation is present in a DNA repair gene, the repair gene will either not be expressed or be expressed in an altered form. Then the repair function will likely be deficient, and, as a consequence, damages will tend to accumulate. Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table.

Inherited DNA repair gene mutations that increase cancer risk DNA repair gene  | Protein  | Repair pathways affected  | Cancers with increased risk

|
|
|

breast cancer 1 & 2  | BRCA1 BRCA2 | HRR of double strand breaks and daughter strand gaps[38] | breast, ovarian [39]
ataxia telangiectasia mutated  | ATM  | Different mutations in ATM reduce HRR, SSA or NHEJ [40] | leukemia, lymphoma, breast [40][41]
Nijmegen breakage syndrome | NBS (NBN) | NHEJ [42] | lymphoid cancers [42]
MRE11A  | MRE11  | HRR and NHEJ [43] | breast [44]
Bloom syndrome | BLM (helicase)  | HRR [45] | leukemia, lymphoma, colon, breast, skin, lung, auditory canal, tongue, esophagus, stomach, tonsil, larynx, uterus [46]
WRN  | WRN  | HRR, NHEJ, long patch BER [47] | soft tissue sarcoma, colorectal, skin, thyroid, pancreas [48]
RECQL4 | RECQ4  | Helicase likely active in HRR [49] | basal cell carcinoma, squamous cell carcinoma, intraepidermal carcinoma [50]
Fanconi anemia genes FANCA, B, C, D1, D2, E, F, G, I, J, L, M, N  | FANCA etc.  | HRR and TLS [51] | leukemia, liver tumors, solid tumors many areas [52]
XPC, XPE (DDB2)  | XPC, XPE  | Global genomic NER, repairs damage in both transcribed and untranscribed DNA [53][54] | skin cancer (melanoma and non-melanoma) [53][54]
XPA, XPB, XPD, XPF, XPG | XPA XPB XPD XPF XPG  | Transcription coupled NER repairs the transcribed strands of transcriptionally active genes [55] | skin cancer (melanoma and non-melanoma) [55]
XPV (also called polymerase H)  | XPV (POLH)  | Translesion synthesis (TLS) [56] | skin cancers (basal cell, squamous cell, melanoma) [56]
mutS (E. coli) homolog 2, mutS (E. coli) homolog 6, mutL (E. coli) homolog 1,

postmeiotic segregation increased 2 (S. cerevisiae)

| MSH2 MSH6 MLH1 PMS2  | MMR [57] | colorectal, endometrial [57]
mutY homolog (E. coli)  | MUTYH  | BER of A paired with 8-oxo-dG [58] | colon [58]
TP53 | P53  | Direct role in HRR, BER, NER and acts in DNA damage response[59] for those pathways and for NHEJ and MMR [60] | sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas [61]
NTHL1  | NTHL1  | BER for Tg, FapyG, 5-hC, 5-hU in dsDNA[62] | Colon cancer, endometrial cancer, duodenal cancer, basal-cell carcinoma[63]

## See also

* Biogerontology
* Degenerative disease
* DNA damage theory of aging
* Genetic disorder
* Senescence

## References

1. ↑ "Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation". Int J Mol Sci 17 (11): 1840. 2016. doi:10.3390/ijms17111840. PMID 27827925.
2. ↑ "Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss". Cell Stem Cell 1 (1): 113–26. 2007. doi:10.1016/j.stem.2007.03.002. PMID 18371340.
3. ↑ "Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice". EMBO Rep. 5 (5): 503–9. 2004. doi:10.1038/sj.embor.7400127. PMID 15105825.
4. ↑ "The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency". PLOS ONE 9 (4). 2014. doi:10.1371/journal.pone.0093568. PMID 24740260. Bibcode: 2014PLoSO...993568R.
5. ↑ "DNA-PKcs deficiency leads to persistence of oxidatively induced clustered DNA lesions in human tumor cells". Free Radic. Biol. Med. 48 (10): 1435–43. 2010. doi:10.1016/j.freeradbiomed.2010.02.033. PMID 20193758.
6. ↑ "XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase". DNA Repair (Amst.) 10 (7): 697–713. 2011. doi:10.1016/j.dnarep.2011.04.028. PMID 21571596.
7. ↑ 7.0 7.1 Cite error: Invalid `<ref>` tag; no text was provided for refs named `Gregg`
8. ↑ "Deficiency in the nuclease activity of xeroderma pigmentosum G in mice leads to hypersensitivity to UV irradiation". Mol. Cell. Biol. 24 (6): 2237–42. 2004. doi:10.1128/MCB.24.6.2237-2242.2004. PMID 14993263.
9. ↑ "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability". Mol. Cell 61 (4): 535–46. 2016. doi:10.1016/j.molcel.2015.12.026. PMID 26833090.
10. ↑ "Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repair enzyme thymine glycol DNA glycosylase". Nucleic Acids Res. 27 (4): 979–83. 1999. doi:10.1093/nar/27.4.979. PMID 9927729.
11. ↑ "Factors influencing the removal of thymine glycol from DNA in γ-irradiated human cells". Factors influencing the removal of thymine glycol from DNA in gamma-irradiated human cells. Progress in Nucleic Acid Research and Molecular Biology. 68. 2001. 139–49. doi:10.1016/S0079-6603(01)68096-6. ISBN 978-0-12-540068-8.
12. ↑ 12.0 12.1 "Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome". J. Mol. Biol. 428 (1): 62–78. 2016. doi:10.1016/j.jmb.2015.11.020. PMID 26616585.
13. ↑ 13.0 13.1 13.2 13.3 "The role of CSA and CSB protein in the oxidative stress response". Mech. Ageing Dev. 134 (5–6): 261–9. 2013. doi:10.1016/j.mad.2013.03.006. PMID 23562424.
14. ↑ "Disruption of TTDA results in complete nucleotide excision repair deficiency and embryonic lethality". PLOS Genet. 9 (4). 2013. doi:10.1371/journal.pgen.1003431. PMID 23637614.
15. ↑ "Slowly progressing nucleotide excision repair in trichothiodystrophy group A patient fibroblasts". Mol. Cell. Biol. 31 (17): 3630–8. 2011. doi:10.1128/MCB.01462-10. PMID 21730288.
16. ↑ 16.0 16.1 "Deletion of Ku80 causes early aging independent of chronic inflammation and Rag-1-induced DSBs". Mech. Ageing Dev. 128 (11–12): 601–8. 2007. doi:10.1016/j.mad.2007.08.006. PMID 17928034.
17. ↑ "DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts". Chromosoma 126 (2): 287–298. 2017. doi:10.1007/s00412-016-0590-9. PMID 27136939.
18. ↑ "Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer". Mol. Cell. Biol. 27 (23): 8205–14. 2007. doi:10.1128/MCB.00785-07. PMID 17875923.
19. ↑ "Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina". The Nuclear Envelope. Methods in Molecular Biology. 1411. 2016. pp. 419–37. doi:10.1007/978-1-4939-3530-7_26. ISBN 978-1-4939-3528-4.
20. ↑ "α-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair". J. Biol. Chem. 289 (23): 16046–56. 2014. doi:10.1074/jbc.M114.558510. PMID 24753253.
21. ↑ "NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging". Mech. Ageing Dev. 146-148: 42–52. 2015. doi:10.1016/j.mad.2015.03.012. PMID 25843235.
22. ↑ 22.0 22.1 "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Res. Rev. 33: 30–35. 2017. doi:10.1016/j.arr.2016.06.002. PMID 27287744.
23. ↑ "The multifaceted functions of sirtuins in cancer". Nat. Rev. Cancer 15 (10): 608–24. 2015. doi:10.1038/nrc3985. PMID 26383140.
24. ↑ Mostoslavsky, R; Chua, KF; Lombard, DB; Pang, WW; Fischer, MR; Gellon, L; Liu, P; Mostoslavsky, G et al. (Jan 2006). "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell 124 (2): 315–29. doi:10.1016/j.cell.2005.11.044. PMID 16439206.
25. ↑ "SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair". EMBO J. 35 (14): 1488–503. 2016. doi:10.15252/embj.201593499. PMID 27225932.
26. ↑ "Roles of Werner syndrome protein in protection of genome integrity". DNA Repair (Amst.) 9 (3): 331–44. 2010. doi:10.1016/j.dnarep.2009.12.011. PMID 20075015.
27. ↑ "RecQ helicases and PARP1 team up in maintaining genome integrity". Ageing Res. Rev. 23 (Pt A): 12–28. 2015. doi:10.1016/j.arr.2014.12.006. PMID 25555679.
28. ↑ "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780–5. 2005. doi:10.1038/nm1266. PMID 15980864.
29. ↑ 29.0 29.1 Best, BP (2009). "Nuclear DNA damage as a direct cause of aging". Rejuvenation Research 12 (3): 199–208. doi:10.1089/rej.2009.0847. PMID 19594328. http://www.benbest.com/lifeext/Nuclear_DNA_in_Aging.pdf. Retrieved 2009-09-29.
30. ↑ "Aging and genome maintenance: lessons from the mouse?". Science 299 (5611): 1355–9. February 2003. doi:10.1126/science.1079161. PMID 12610296.
31. ↑ "Activation of human MutS homologs by 8-oxo-guanine DNA damage". J. Biol. Chem. 277 (10): 8260–6. March 2002. doi:10.1074/jbc.M111269200. PMID 11756455.
32. ↑ Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009 Oct 8;361(15):1475-85.
33. ↑ "Defective DNA repair and neurodegenerative disease". Cell 130 (6): 991–1004. September 2007. doi:10.1016/j.cell.2007.08.043. PMID 17889645.
34. ↑ Miller RA (April 2004). "'Accelerated aging': a primrose path to insight?". Aging Cell 3 (2): 47–51. doi:10.1111/j.1474-9728.2004.00081.x. PMID 15038817. https://deepblue.lib.umich.edu/bitstream/2027.42/73065/1/j.1474-9728.2004.00081.x.pdf.
35. ↑ "Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity". Aging Cell 3 (2): 55–65. April 2004. doi:10.1111/j.1474-9728.2004.00082.x. PMID 15038819.
36. ↑ "Rebuttal to Miller: 'Accelerated aging': a primrose path to insight?'". Aging Cell 3 (2): 67–9. April 2004. doi:10.1111/j.1474-9728.2004.00087.x. PMID 15038820.
37. ↑ Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat Res. 2002 Jun;511(2):145-78. Review.
38. ↑ "Minding the gap: the underground functions of BRCA1 and BRCA2 at stalled replication forks". DNA Repair (Amst.) 6 (7): 1018–31. 2007. doi:10.1016/j.dnarep.2007.02.020. PMID 17379580.
39. ↑ "Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions". Gynecol. Oncol. 136 (1): 3–7. 2015. doi:10.1016/j.ygyno.2014.09.009. PMID 25238946.
40. ↑ 40.0 40.1 "Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways". FASEB J. 25 (11): 3849–60. 2011. doi:10.1096/fj.11-185546. PMID 21778326.
41. ↑ "Recombinational DNA repair and human disease". Mutat. Res. 509 (1–2): 49–78. 2002. doi:10.1016/s0027-5107(02)00224-5. PMID 12427531. Bibcode: 2002MRFMM.509...49T. https://zenodo.org/record/1259665.
42. ↑ 42.0 42.1 "Nijmegen breakage syndrome (NBS)". Orphanet J Rare Dis 7: 13. 2012. doi:10.1186/1750-1172-7-13. PMID 22373003.
43. ↑ "After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available". J. Cell Sci. 117 (Pt 21): 4935–45. 2004. doi:10.1242/jcs.01355. PMID 15367581.
44. ↑ "Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene". Mol Oncol 2 (4): 296–316. 2008. doi:10.1016/j.molonc.2008.09.007. PMID 19383352.
45. ↑ "Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair". Proc. Natl. Acad. Sci. U.S.A. 105 (44): 16906–11. 2008. doi:10.1073/pnas.0809380105. PMID 18971343. Bibcode: 2008PNAS..10516906N.
46. ↑ "Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients". Am. J. Hum. Genet. 21 (2): 196–227. 1969. PMID 5770175.
47. ↑ "Deficient DNA repair in the human progeroid disorder, Werner syndrome". Mutat. Res. 577 (1–2): 252–9. 2005. doi:10.1016/j.mrfmmm.2005.03.021. PMID 15916783. Bibcode: 2005MRFMM.577..252B. https://zenodo.org/record/1259235.
48. ↑ "Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology". Semin. Cancer Biol. 20 (5): 329–39. 2010. doi:10.1016/j.semcancer.2010.10.002. PMID 20934517.
49. ↑ "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". Biogerontology 10 (3): 235–52. 2009. doi:10.1007/s10522-008-9205-z. PMID 19083132.
50. ↑ "Two primary osteosarcomas in a patient with Rothmund-Thomson syndrome". Clin. Orthop. Relat. Res. 378 (378): 213–23. 2000. doi:10.1097/00003086-200009000-00032. PMID 10986997.
51. ↑ "Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights". Mutat. Res. 668 (1–2): 54–72. 2009. doi:10.1016/j.mrfmmm.2009.02.003. PMID 19622404. Bibcode: 2009MRFMM.668...54T.
52. ↑ "Cancer in Fanconi anemia, 1927-2001". Cancer 97 (2): 425–40. 2003. doi:10.1002/cncr.11046. PMID 12518367.
53. ↑ 53.0 53.1 "Xeroderma pigmentosum". Orphanet J Rare Dis 6: 70. 2011. doi:10.1186/1750-1172-6-70. PMID 22044607.
54. ↑ 54.0 54.1 "Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells". Photochem. Photobiol. 87 (3): 729–33. 2011. doi:10.1111/j.1751-1097.2011.00909.x. PMID 21388382.
55. ↑ 55.0 55.1 "DNA repair diseases: What do they tell us about cancer and aging?". Genet. Mol. Biol. 37 (1 Suppl): 220–33. 2014. doi:10.1590/s1415-47572014000200008. PMID 24764756.
56. ↑ 56.0 56.1 "Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations". Hum. Mutat. 35 (1): 117–28. 2014. doi:10.1002/humu.22462. PMID 24130121.
57. ↑ 57.0 57.1 "Endometrial cancer and Lynch syndrome: clinical and pathologic considerations". Cancer Control 16 (1): 14–22. 2009. doi:10.1177/107327480901600103. PMID 19078925.
58. ↑ 58.0 58.1 "MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA". Front Genet 4: 18. 2013. doi:10.3389/fgene.2013.00018. PMID 23450852.
59. ↑ "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol. Cancer Res. 6 (4): 517–24. 2008. doi:10.1158/1541-7786.MCR-08-0020. PMID 18403632.
60. ↑ "The role of p53 in treatment responses of lung cancer". Biochem. Biophys. Res. Commun. 331 (3): 868–80. 2005. doi:10.1016/j.bbrc.2005.03.192. PMID 15865943.
61. ↑ "Connecting molecular pathways to hereditary cancer risk syndromes". Am Soc Clin Oncol Educ Book 33: 81–90. 2013. doi:10.1200/EdBook_AM.2013.33.81. PMID 23714463.
62. ↑ "Base excision repair". Cold Spring Harb Perspect Biol 5 (4). 2013. doi:10.1101/cshperspect.a012583. PMID 23545420.
63. ↑ "NTHL1 defines novel cancer syndrome". Oncotarget 6 (33): 34069–70. 2015. doi:10.18632/oncotarget.5864. PMID 26431160.

## External links

Classification|

* MeSH: D049914

|

* BRCA - Companion Reviews and Search Terms
* BRCA1 - Companion Reviews and Search Terms
* BRCA2 - Companion Reviews and Search Terms
* ATM - Companion Reviews and Search Terms
* NBS1 - Companion Reviews and Search Terms
* Bloom s syndrome - Companion Reviews and Search Terms
* Fanconi s anemia - Companion Reviews and Search Terms
* WRN - Companion Reviews and Search Terms
* RECQ- Companion Reviews and Search Terms
* RECQL4 - Companion Reviews and Search Terms
* FANCJ - Companion Reviews and Search Terms
* FANCM - Companion Reviews and Search Terms
* FANCN - Companion Reviews and Search Terms
* XPB - Companion Reviews and Search Terms
* XPD - Companion Reviews and Search Terms
* XPG - Companion Reviews and Search Terms
* MSH6 - Companion Reviews and Search Terms
* MUTYH - Companion Reviews and Search Terms
* DNA repair and toxicology - Companion Reviews and Search Terms
* Neoplasia inherited - Companion Reviews and Search Terms
* Neoplasia carcinogenesis - Companion Reviews and Search Terms
* Segmental Progeria

* v
* t
* e

Congenital malformations and deformations of integument / skin disease

Genodermatosis|

| Congenital ichthyosis/
erythrokeratodermia|

| AD|

* Ichthyosis vulgaris

|

AR|

* Congenital ichthyosiform erythroderma: Epidermolytic hyperkeratosis]]
* Lamellar ichthyosis
* Harlequin-type ichthyosis

* Netherton syndrome
* Zunich–Kaye syndrome
* Sjögren–Larsson syndrome

XR|

* X-linked ichthyosis

Ungrouped|

* Ichthyosis bullosa of Siemens
* Ichthyosis follicularis
* Ichthyosis prematurity syndrome
* Ichthyosis–sclerosing cholangitis syndrome
* Nonbullous congenital ichthyosiform erythroderma
* Ichthyosis linearis circumflexa
* Ichthyosis hystrix

and related|

* EBS
* EBS-K
* EBS-WC
* EBS-DM
* EBS-OG
* EBS-MD
* EBS-MP

* JEB
* JEB-H
* Mitis
* Generalized atrophic
* JEB-PA

* DEB
* DDEB
* RDEB

* related: Costello syndrome
* Kindler syndrome
* Laryngoonychocutaneous syndrome
* Skin fragility syndrome

Ectodermal dysplasia|

* Naegeli syndrome/Dermatopathia pigmentosa reticularis
* Hay–Wells syndrome
* Hypohidrotic ectodermal dysplasia
* Focal dermal hypoplasia
* Ellis–van Creveld syndrome
* Rapp–Hodgkin syndrome/Hay–Wells syndrome

Elastic/Connective|

* Ehlers–Danlos syndromes
* Cutis laxa (Gerodermia osteodysplastica)
* Popliteal pterygium syndrome
* Pseudoxanthoma elasticum
* Van der Woude syndrome

Hyperkeratosis/
keratinopathy|

| PPK|

* diffuse: Diffuse epidermolytic palmoplantar keratoderma
* Diffuse nonepidermolytic palmoplantar keratoderma
* Palmoplantar keratoderma of Sybert
* Meleda disease

* syndromic
* connexin
* Bart–Pumphrey syndrome
* Clouston's hidrotic ectodermal dysplasia
* Vohwinkel syndrome
* Corneodermatoosseous syndrome
* plakoglobin
* Naxos syndrome
* Scleroatrophic syndrome of Huriez
* Olmsted syndrome
* Cathepsin C
* Papillon–Lefèvre syndrome
* Haim–Munk syndrome
* Camisa disease
* focal: Focal palmoplantar keratoderma with oral mucosal hyperkeratosis
* Focal palmoplantar and gingival keratosis
* Howel–Evans syndrome
* Pachyonychia congenita
* Pachyonychia congenita type I
* Pachyonychia congenita type II
* Striate palmoplantar keratoderma
* Tyrosinemia type II

* punctate: Acrokeratoelastoidosis of Costa
* Focal acral hyperkeratosis
* Keratosis punctata palmaris et plantaris
* Keratosis punctata of the palmar creases
* Schöpf–Schulz–Passarge syndrome
* Porokeratosis plantaris discreta
* Spiny keratoderma

* ungrouped: Palmoplantar keratoderma and spastic paraplegia
* desmoplakin
* Carvajal syndrome
* connexin
* Erythrokeratodermia variabilis
* HID/KID

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Other|

* Meleda disease
* Keratosis pilaris
* ATP2A2
* Darier's disease
* Dyskeratosis congenita
* Lelis syndrome

* Dyskeratosis congenita
* Keratolytic winter erythema
* Keratosis follicularis spinulosa decalvans
* Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome
* Keratosis pilaris atrophicans faciei
* Keratosis pilaris

Other|

* cadherin
* EEM syndrome
* immune system
* Hereditary lymphedema
* Mastocytosis/Urticaria pigmentosa
* Hailey–Hailey

see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder

Developmental
anomalies|

| Midline|

* Dermoid cyst
* Encephalocele
* Nasal glioma
* PHACE association
* Sinus pericranii

|

Nevus|

* Capillary hemangioma
* Port-wine stain
* Nevus flammeus nuchae

Other/ungrouped|

* Aplasia cutis congenita
* Amniotic band syndrome
* Branchial cyst
* Cavernous venous malformation

* Accessory nail of the fifth toe
* Bronchogenic cyst
* Congenital cartilaginous rest of the neck
* Congenital hypertrophy of the lateral fold of the hallux
* Congenital lip pit
* Congenital malformations of the dermatoglyphs
* Congenital preauricular fistula
* Congenital smooth muscle hamartoma
* Cystic lymphatic malformation
* Median raphe cyst
* Melanotic neuroectodermal tumor of infancy
* Mongolian spot
* Nasolacrimal duct cyst
* Omphalomesenteric duct cyst
* Poland anomaly
* Rapidly involuting congenital hemangioma
* Rosenthal–Kloepfer syndrome
* Skin dimple
* Superficial lymphatic malformation
* Thyroglossal duct cyst
* Verrucous vascular malformation
* Birthmark

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Original source: https://en.wikipedia.org/wiki/DNA repair-deficiency disorder. Read more

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