- DNA repair-deficiency disorder
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DNA repair-deficiency disorder Classification and external resources MeSH D049914 A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.
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.
Contents
Examples
Some of the examples include:
- Ataxia telangiectasia[1]
- Bloom syndrome
- Cockayne's syndrome
- Fanconi's anaemia
- Progeria (Hutchinson-Gilford Progeria syndrome)[2][3]
- Rothmund-Thomson syndrome[4][5]
- Trichothiodystrophy[6]
- Werner syndrome
- Xeroderma pigmentosum
DNA repair defects distinguished from "accelerated aging"
Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (usually some of both).[7] 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")[8]. 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"[9]. Some DNA repair defects manifest as neurodegeneration rather than as cancer or "accelerated aging"[10].
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[11].
Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage.[7] The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging"[12]. 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[13].
See also
- Biogerontology
- Degenerative disease
- Genetic disorder
- Senescence
References
- ^ Biton S, Dar I, Mittelman L, Pereg Y, Barzilai A, Shiloh Y (June 2006). "Nuclear ataxia-telangiectasia mutated (ATM) mediates the cellular response to DNA double strand breaks in human neuron-like cells". J. Biol. Chem. 281 (25): 17482–91. doi:10.1074/jbc.M601895200. PMID 16627474. http://www.jbc.org/cgi/content/full/281/25/17482.
- ^ Manju K, Muralikrishna B, Parnaik VK (July 2006). "Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci". J. Cell. Sci. 119 (Pt 13): 2704–14. doi:10.1242/jcs.03009. PMID 16772334. http://jcs.biologists.org/cgi/content/full/119/13/2704.
- ^ Scaffidi P, Misteli T (May 2006). "Lamin A-dependent nuclear defects in human aging". Science 312 (5776): 1059–63. doi:10.1126/science.1127168. PMC 1855250. PMID 16645051. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1855250.
- ^ Brosh RM, Bohr VA (2007). "Human premature aging, DNA repair and RecQ helicases". Nucleic Acids Res. 35 (22): 7527–44. doi:10.1093/nar/gkm1008. PMC 2190726. PMID 18006573. http://nar.oxfordjournals.org/cgi/content/full/35/22/7527.
- ^ Kitao S, Shimamoto A, Goto M, et al. (May 1999). "Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome". Nat. Genet. 22 (1): 82–4. doi:10.1038/8788. PMID 10319867.
- ^ Kleijer WJ, Laugel V, Berneburg M, et al. (May 2008). "Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy". DNA Repair (Amst.) 7 (5): 744–50. doi:10.1016/j.dnarep.2008.01.014. PMID 18329345. http://linkinghub.elsevier.com/retrieve/pii/S1568-7864(08)00042-6.
- ^ a b 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.
- ^ Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J (February 2003). "Aging and genome maintenance: lessons from the mouse?". Science 299 (5611): 1355–9. doi:10.1126/science.1079161. PMID 12610296.
- ^ Mazurek A, Berardini M, Fishel R (March 2002). "Activation of human MutS homologs by 8-oxo-guanine DNA damage". J. Biol. Chem. 277 (10): 8260–6. doi:10.1074/jbc.M111269200. PMID 11756455. http://www.jbc.org/cgi/content/full/277/10/8260.
- ^ Rass U, Ahel I, West SC (September 2007). "Defective DNA repair and neurodegenerative disease". Cell 130 (6): 991–1004. doi:10.1016/j.cell.2007.08.043. PMID 17889645.
- ^ 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.
- ^ Hasty P, Vijg J (April 2004). "Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity". Aging Cell 3 (2): 55–65. doi:10.1111/j.1474-9728.2004.00082.x. PMID 15038819.
- ^ Hasty P, Vijg J (April 2004). "Rebuttal to Miller: 'Accelerated aging': a primrose path to insight?'". Aging Cell 3 (2): 67–9. doi:10.1111/j.1474-9728.2004.00087.x. PMID 15038820.
External links
Metabolic disease: DNA replication and DNA repair-deficiency disorder DNA replication Separation/initiation: RNASEH2A (Aicardi–Goutières syndrome 4)
Termination/telomerase: DKC1 (Dyskeratosis congenita)DNA repair Cockayne syndrome/DeSanctis–Cacchione syndrome · Thymine dimer (Xeroderma pigmentosum) · IBIDS syndromeOtherRecQ helicase (Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome/Rapadilino syndrome) · Fanconi anemia · Li-Fraumeni syndrome · Severe combined immunodeficiencysee also DNA replication, DNA repair
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfkCongenital malformations and deformations of integument / skin disease (Q80–Q82, 757.0–757.3) Genodermatosis Congenital ichthyosis/
erythrokeratodermiaADARUngroupedIchthyosis bullosa of Siemens · Ichthyosis follicularis · Ichthyosis prematurity syndrome · Ichthyosis–sclerosing cholangitis syndrome · Nonbullous congenital ichthyosiform erythroderma · Ichthyosis linearis circumflexa · Ichthyosis hystrixEB
and relatedJEB (JEB-H, Mitis, Generalized atrophic, JEB-PA)related: Costello syndrome · Kindler syndrome · Laryngoonychocutaneous syndrome · Skin fragility syndrome ·Naegeli syndrome/Dermatopathia pigmentosa reticularis · Hay–Wells syndrome · Hypohidrotic ectodermal dysplasia · Focal dermal hypoplasia · Ellis–van Creveld syndrome · Rapp–Hodgkin syndrome/Hay–Wells syndromeEhlers–Danlos syndrome · Cutis laxa (Gerodermia osteodysplastica) · Popliteal pterygium syndrome · Pseudoxanthoma elasticum · Van Der Woude syndromeHyperkeratosis/
keratinopathydiffuse: Diffuse epidermolytic palmoplantar keratoderma • Diffuse nonepidermolytic palmoplantar keratoderma • Palmoplantar keratoderma of Sybert • Mal de Meleda •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 diseasefocal: 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 keratodermaungrouped: Palmoplantar keratoderma and spastic paraplegia • desmoplakin (Carvajal syndrome) • connexin (Erythrokeratodermia variabilis • HID/KID)OtherMeleda disease · Keratosis pilaris · ATP2A2 (Darier's disease) · Dyskeratosis congenita · Lelis syndromeDyskeratosis congenita · Keratolytic winter erythema · Keratosis follicularis spinulosa decalvans · Keratosis linearis with ichthyosis congenital and sclerosing keratoderma syndrome · Keratosis pilaris atrophicans faciei · Keratosis pilarisOthercadherin (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 disorderDevelopmental
anomaliesMidlineOther/ungroupedAplasia 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 · BirthmarkCategories:- Causes of death
- DNA replication and repair-deficiency disorders
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