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a mild form of ichthyosis characterized by abnormal dryness and roughness of the skin (同)xerodermia

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/27 15:19:51」(JST)

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Child suffering from xeroderma pigmentosum in Rukum, Nepal

Xeroderma pigmentosum has an autosomal recessive pattern of inheritance.

Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient.^[2]^:574 In extreme cases, all exposure to sunlight must be forbidden, no matter how small; as such, individuals with the disease are often colloquially referred to as Children of the Night.^[3] Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. In fact, metastatic malignant melanoma and squamous cell carcinoma^[4] are the two most common causes of death in XP victims. This disease involves both sexes and all races, with an incidence of 1:250,000 in the United States.^[5] XP is roughly six times more common in Japanese people^[4] than in other groups.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers, namely cyclobutane-pyrimidine dimers and pyrimidine-6-4-pyrimidone photoproducts. In a healthy, normal human being, the damage is first excised by endonucleases. DNA polymerase then repairs the missing sequence, and ligase "seals" the transaction. This process is known as nucleotide excision repair.

Genetics

One of the most frequent defects in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.^[6] If left unchecked, damage caused by ultraviolet light can cause mutations in individual cell's DNA. The causes of the neurological abnormalities are poorly understood and are not connected with exposure to ultraviolet light. The most current theories suggest that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some types of this damage must be repaired by NER^[7]

Since DNA repair is under genetic control, it can easily undergo mutations. Many genetic disorders such as xeroderma pigmentosum (XP; MIM 278700) are caused by mutations in genes that repair DNA.^[7] If the gene was not repaired correctly it could cause xeroderma pigmentosum in individuals. The autosomal recessive disorder xeroderma pigmentosum or XP has a frequency of 1 in every 250,000 individuals of all races and ethnic groups.^[8] Those affected with the autosomal recessive disorder XP are extremely sensitive to UV light produced by the sun and even with a short exposure to it causes dry, flaking skin and pigmented spots that can develop into skin cancer. Individuals with XP are about 1,000 times more likely to develop skin cancer than individuals without the disorder.

The molecular defects in XP cells result in a greatly elevated induction of mutations in sun-exposed skin of affected individuals. This increased mutation frequency probably accounts for the pigmentation changes and the skin cancers. Examination of mutations in the p53 gene in tumors from XP patients reveal p53 mutations characteristic of UV exposure in the majority of tumors^[8] As with all genetic disorders, genetic counseling and psychological support is appropriate for the families, to discuss probability of occurrence in future pregnancies, feelings of isolation and concern about career prospects. Although there is no cure for xeroderma pigmentosum, the effects can be minimized by getting protection from the sunlight and if possible early removal of precancerous lesions. The most common fate for individuals with XP is early death from cancer due to the fact that they need to take outstanding measures to protect themselves from the dangers of the UV light. But if there is an absence of neurological problems and are always protected or away from the sunlight, the prognosis is good.

Types

There are seven complementation groups, plus one variant form:

Type	Diseases Database	OMIM	Gene	Locus	Also known as/Description
Type A, I, XPA	29877	278700	XPA	9q22.3	Xeroderma pigmentosum group A - the classical form of XP
Type B, II, XPB	29878	133510	XPB	2q21	Xeroderma pigmentosum group B
Type C, III, XPC	29879	278720	XPC	3p25	Xeroderma pigmentosum group C
Type D, IV, XPD	29880	278730 278800	XPD ERCC6	19q13.2-q13.3, 10q11	Xeroderma pigmentosum group D or De Sanctis-Cacchione syndrome (can be considered a subtype of XPD)
Type E, V, XPE	29881	278740	DDB2	11p12-p11	Xeroderma pigmentosum group E
Type F, VI, XPF	29882	278760	ERCC4	16p13.3-p13.13	Xeroderma pigmentosum group F
Type G, VII, XPG	29883	278780 133530	RAD2 ERCC5	13q33	Xeroderma pigmentosum group G and COFS syndrome type 3
Type V, XPV		278750	POLH	6p21.1-p12	Xeroderma pigmentosum variant - these patients suffer from mutation in a gene that codes for a specialized DNA polymerase called polymerase-η (eta). Polymerase-η can replicate over the damage and is needed when cells enter S-phase in the presence of a DNA-replication.

Symptoms

Symptoms include:

Severe sunburn when exposed to only small amounts of sunlight. These often occur during a child's first exposure to sunlight.
Development of many freckles at an early age
Rough-surfaced growths (solar keratoses), and skin cancers
Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded
Blistering or freckling on minimum sun exposure
Spider Veins
Limited growth of hair on chest and legs
Scaly skin
Dry skin
Irregular dark spots on the skin
Corneal ulcerations

Treatment

The most obvious, and often important part of treatment, is avoiding exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil.^[1]

Prognosis

Fewer than 40% of individuals with the disease survive beyond the age of 20. Some XP victims with less severe cases do manage to live well into their 40s.

In popular culture

These fictional characters have XP:

Christopher Snow in Dean Koontz's Moonlight Bay Trilogy
1994 CBS-TV movie Children of the Dark is based on XP.
Luke in the 2002 novel Going Out by Scarlett Thomas
In the Channel 4 series Ultraviolet, one of the humans is mistaken for a vampire because he avoids sunlight, when in fact he has XP.
In the book The Lucifer Code (originally published in 1997 as "Lucifer") the character Bradley Soames suffers from XP, and wears an all-encompassing "suit" complete with mask, hood and heavily tinted lenses in order to venture outdoors.
In the independent film Dark Side of the Sun (1988) with Brad Pitt as the main character suffering from XP.
In the 2001 film The Others, the two children, Anne and Nicholas, suffer from XP.
In the 2003 novel Second Glance by Jodi Picoult, Ethan Wakeman, the 9-year-old nephew of Ross Wakeman (the main protagonist)
The 2003 Angela Johnson novel, A Cool Moonlight, centers on a girl who has XP and can never be in the sun. The family has gone to drastic measures to help make her life easier, and to make her feel like a normal 8-year-old.
The 2006 Japanese drama "Taiyou no uta"(A Song to the Sun) centers around a girl with XP who dreams of being a singer.
The 2006 German film Mondscheinkinder (Children of the Moonlight) features 12-year-old Lisa who creates a fantasy world for her 6 year old brother Paul, who has XP and cannot leave the house. Their special relationship is threatened when Lisa gets her first boyfriend, facing her with hard choices.^[9]
The Spanish film "Eskalofrío" or "Shiver" released in 2008 featured a main character named Santi who is ostracized as he suffers from the condition.
The 2011 film La permission de minuit by French director Delphine Gleize centers on a teenage boy with XP.
The 2012 documentary "Sun Kissed" explores the XP problem on the Navajo Indian Reservation.

The 2013 young adult novel What We Saw at Night by Jacquelyn Mitchard tells the story of three teenagers who are suffering from this disease, go out only when dark and witness something strange one night.
The 2013 middle grade novel "Doom & Gloom" by M. J. Shaughnessy tells the story of a twelve-year-old boy who triumphs over his disease by donning a protective solar suit and becoming a superhero.

The 2014 adult fiction book The Deepest Secret by Carla Buckley tells the story of a mother with a son who has XP and the lengths she will go to in order to protect him from a crisis that threatens to tear the community apart.^[10]

References

^ ^a ^b Halpern, J.; Hopping, B.; Brostoff, J. (2008). "Photosensitivity, corneal scarring and developmental delay: Xeroderma Pigmentosum in a tropical country". Cases journal 1 (1): 254. doi:10.1186/1757-1626-1-254. PMC 2577106. PMID 18937855.
^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
^ Medical Biochemistry at a Glance. John Wiley & Sons. 28 November 2011. ISBN 1118292405. Retrieved 17 June 2011. Xeroderma pigmentosa is a rare, autosomal recessive disease caused by a defective UV-specific endonuclease. Patients with mutations are unable to repair DNA damage caused by sunlight and have been described as "children of the night."
^ ^a ^b Li, Lei (January 8, 2007). "Chapter 3 Nucleotide Excision Repair". DNA REPAIR, GENETIC INSTABILITY, AND CANCER. World Scientific Publishing. pp. 75–76. ISBN 981-270-014-5.
^ Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet J Rare Dis 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607.
^ E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 1118. ISBN 978-1-55581-319-2.
^ ^a ^b Brooks PJ DNA Repair (Amst). 2014 March 2; 7(7):1168-79.
^ ^a ^b Daya-Grosjean L, Sarasin A Mutat Res. 2014 March 2; 571(1-2):43-56
^ See the website of the movie, in German: http://www.mondscheinkinder-der-film.de/
^ https://www.goodreads.com/book/show/18248415-the-deepest-secret?ac=1

External links

Information

GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum
An article about this disorder from DigiLander.iol.it (in English and Italian)
Cancer.Net Xeroderma Pigmentosum
DermNet systemic/xeroderma-pigmentosum

Charities

XP Society
XP Family Support Group
UK Patient Support Group

Short films

Sloan Science and Film / Short Films / XP by David Barba 10 minutes
Web Site of a Short Film about an xeroderma pigmentosum (XP) Patient. Film is directed by Kimberly Williams-Paisley

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 色素性乾皮症 xeroderma pigmentosum
2. 遺伝性皮膚疾患：概要 the genodermatoses an overview
3. 遺伝性疾患に伴う神経障害 neuropathies associated with hereditary disorders
4. 皮膚扁平上皮癌の疫学および危険因子 epidemiology and risk factors for cutaneous squamous cell carcinoma
5. 光線過敏症（光線皮膚症）：臨床症状、診断、および治療 photosensitivity disorders photodermatoses clinical manifestations diagnosis and treatment

English Journal

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis.

Liu D1, Wu D1, Li H2, Dong M3.Author information 1Department of pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.2Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.3Department of pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China. Electronic address: mdhappy2006@hotmail.com.AbstractAIMS: Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.
Gene.Gene.2014 Apr 1;538(2):209-216. doi: 10.1016/j.gene.2014.01.049. Epub 2014 Jan 28.
AIMS: Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence inte
PMID 24486506

A nonsense mutation in the Xeroderma pigmentosum complementation group F (XPF) gene is associated with gastric carcinogenesis.

Wei ZH1, Guo WH1, Wu J1, Suo WH1, Fu GH2.Author information 1Pathology Center, Shanghai First People's Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.2Pathology Center, Shanghai First People's Hospital / Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address: fuguhu@263.net.AbstractXPF/ERCC1 endonuclease is required for DNA lesion repair. To assess effects of a C2169A nonsense mutation in XPF at position 2169 in gastric cancer tissues and cell lines, genomic DNA was extracted from blood samples of 488 cancer patients and 64 gastric tumors. The mutation was mapped using a TaqMan MGB probe. In addition, gastric cancer cell lines were transfected with mutated XPF to explore XPF/ERCC1 interaction, XPF degradation, and DNA repair by a comet assay. The C2169A mutation was not detected in 488 samples of blood genomic DNA, yet was found in 32 of 64 gastric cancer tissue samples (50.0%), resulting in a 194C-terminal amino acid loss in XPF protein and lower expression. Laser micro-dissection confirmed that this point mutation was not present in surrounding normal tissues from the same patients. The truncated form of XPF (tXPF) impaired interaction with ERCC1, was rapidly degraded via ubiquitination, and resulted in reduced DNA repair. In gastric cancers, the mutation was monoallelic, indicating that XPF is a haplo-insufficient DNA repair gene. As the C2169A mutation is closely associated with gastric carcinogenesis in the Chinese population, our findings shine light on it as a therapeutic target for early diagnosis and treatment of gastric cancer.
Gene.Gene.2014 Mar 10;537(2):238-44. doi: 10.1016/j.gene.2013.12.061. Epub 2014 Jan 8.
XPF/ERCC1 endonuclease is required for DNA lesion repair. To assess effects of a C2169A nonsense mutation in XPF at position 2169 in gastric cancer tissues and cell lines, genomic DNA was extracted from blood samples of 488 cancer patients and 64 gastric tumors. The mutation was mapped using a TaqMa
PMID 24412486

The Structure of Social Exchange in Self-help Support Groups: Development of a Measure.

Brown LD1, Tang X, Hollman RL.Author information 1University of Texas School of Public Health, 1101 N. Campbell, Room 409, El Paso, TX, 79902, USA, louis.d.brown@uth.tmc.edu.AbstractSelf-help support groups are indigenous community resources designed to help people manage a variety of personal challenges, from alcohol abuse to xeroderma pigmentosum. The social exchanges that occur during group meetings are central to understanding how people benefit from participation. This paper examines the different types of social exchange behaviors that occur during meetings, using two studies to develop empirically distinct scales that reliably measure theoretically important types of exchange. Resource theory informed the initial measurement development efforts. Exploratory factor analyses from the first study led to revisions in the factor structure of the social exchange scales. The revised measure captured the exchange of emotional support, experiential information, humor, unwanted behaviors, and exchanges outside meetings. Confirmatory factor analyses from a follow-up study with a different sample of self-help support groups provided good model fit, suggesting the revised structure accurately represented the data. Further, the scales demonstrated good convergent and discriminant validity with related constructs. Future research can use the scales to identify aspects of social exchange that are most important in improving health outcomes among self-help support group participants. Groups can use the scales in practice to celebrate strengths and address weaknesses in their social exchange dynamics.
American journal of community psychology.Am J Community Psychol.2014 Mar;53(1-2):83-95. doi: 10.1007/s10464-013-9621-3.
Self-help support groups are indigenous community resources designed to help people manage a variety of personal challenges, from alcohol abuse to xeroderma pigmentosum. The social exchanges that occur during group meetings are central to understanding how people benefit from participation. This pap
PMID 24398622

Japanese Journal

小児の湿疹・皮膚炎群および色素性乾皮症への低刺激性サンスクリーン剤の臨床的安全性評価

鈴木律子,安本美奈子,福永淳,錦織千佳子,佐々木りか子
日本小児皮膚科学会雑誌 = Journal of pediatric dermatology 30(1), 31-36, 2011-02-28
NAID 10027866876

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions.

Hirota Kouji,Sonoda Eiichiro,Kawamoto Takuo,Motegi Akira,Masutani Chikahide,Hanaoka Fumio,Szüts Dávid,Iwai Shigenori,Sale Julian E,Lehmann Alan,Takeda Shunichi
PLoS genetics 6(10), 2010-10
… We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη(-/-)/POLζ(-/-) cells from the chicken DT40 cell line. …
NAID 120002661519

Related Pictures

★リンクテーブル★

リンク元	「毛細血管拡張性運動失調症」「ファンコニー貧血」「色素性乾皮症」
拡張検索	「xeroderma pigmentosum group A protein」「xeroderma pigmentosum group D protein」
関連記事	「xeroderma」

「毛細血管拡張性運動失調症」

Xeroderma pigmentosum
	An eight-year-old girl from Guatemala with xeroderma pigmentosum
Classification and external resources
ICD-10	Q82.1
ICD-9	757.33
DiseasesDB	14198
MedlinePlus	001467
eMedicine	derm/462 neuro/399
Patient UK	Xeroderma pigmentosum
MeSH	D014983

　　[★]

英: ataxia telangiectasia, AT
同: 血管拡張性運動失調症、毛細血管拡張性運動失調、[毛細血管拡張性小脳失調症]]、ルイ・バー症候群 ルイ・バール症候群 Louis-Bar症候群 Louis-Bar syndrome
関: 免疫不全症候群、脊髄小脳変性症、小脳失調

[show details]

毛細血管拡張性運動失調 : 約 29,200 件
毛細血管拡張性小脳失調症 : 96 件
血管拡張性失調症 : 約 33,100 件
血管拡張性小脳失調症 : 約 4,520 件
毛細血管拡張運動失調 : 38 件
毛細管拡張性運動失調 : 34 件
毛細管拡張性運動失調症 : 28 件
毛細管拡張性運動失調症候群 : 1 件
ルイ・バー症候群 : 50 件
ルイ・バール症候群 : 44 件
ルイ・バル症候群 : nothing
ルイス・バー症候群 : 22 件
ルイス・バール症候群 : nothing
ルイス・バル症候群 : 15 件

概念

ATM遺伝子の異常による
副鼻腔肺感染症、中枢神経障害、毛細血管拡張

結膜、耳介などの毛細血管拡張症、小脳失調症、免疫不全、悪性腫瘍の合併

遺伝

常染色体劣性遺伝

FAMILIAL CANCER SYNDROME
AR: DNA repair abnormalities

xeroderma pigmentosum

Fanconi's anemia

ataxia telangiectasia

病因

ATM遺伝子の異常

ATM蛋白は細胞周期制御、DNA調節に関与していると考えられ、欠損により(in vitroで？)放射線高感受性、細胞周期の異常、染色体脆弱性が認められる

病態

T細胞	B細胞	抗体
T細胞	B細胞	IgM	IgA	IgE	IgG
→↓(漸減)	→	↑(単量体)	↓	↓	↓

症状

SPE.279

神経症状：進行性の小脳失調
血管：毛細血管拡張が3-6歳で出現
感染症：肺炎、気管支炎、気管支拡張症などの呼吸器感染症が多い
悪性腫瘍：原発性免疫不全症の中では本疾患で最多

検査

血液生化学：AFP上昇
免疫血清学検査：T細胞減少、IgA,IgE減少。IgG2,IgG4も減少
細胞遺伝学的検査：放射線に対するDNA修復障害、染色体脆弱性(染色体切断症候群)　　→　　DNA、染色体を障害する治療、薬物投与は避ける

参考

1. ATAXIA-TELANGIECTASIA MUTATED GENE; ATM - OMIM

http://omim.org/entry/607585

2. [charged] Ataxia-telangiectasia - uptodate [1]

「ファンコニー貧血」

　　[★]

英: Fanconi anemia Fanconi's anemia FA
同: ファンコニ貧血、ファンコニ貧血症、ファンコーニ貧血症、Fanconi貧血、ファンコニー貧血症、ファンコニー貧血; ファンコーニ汎血球減少 Fanconi pancytopenia
関: 再生不良性貧血、染色体切断症候群

[show details]

ファンコニ貧血 : 約 3,560 件
ファンコニ貧血症 : 55 件
ファンコーニ貧血 : 約 1,830 件
ファンコーニ貧血症 : 13 件
ファンコニー貧血 : 約 30,000 件
ファンコニー貧血症 : 35 件

概念

先天性再生不良性貧血。
進行性の汎血球減少と低身長、小頭症などの多発奇形や、皮膚の色素沈着、性器発育不全、白血病や各種の悪性腫瘍の易罹患傾向
橈骨側の異常
(1)骨髄不全、(2)先天奇形、(3)皮膚の色素沈着、(4)低身長、(5)性腺機能不全を特徴とする常染色体劣性遺伝の疾患(PED.1122)
貧血の発症は4-6歳。(医学事典)

病因

DNAの修復機構の異常により、細胞のアポトーシスが起こりやすくなるため

相補群による分類

FANCA
FANCB
FANCC
FANCD
FANCE
FANCF
FANCG
FANCX?

疫学

遺伝形式

常染色体性劣性遺伝

FAMILIAL CANCER SYNDROME
AR: DNA repair abnormalities

xeroderma pigmentosum

Fanconi's anemia

ataxia telangiectasia

病変形成＆病理

症状

奇形：母指欠損、橈骨の欠損または低形成、側弯症、先天股脱。　第1指奇形など橈側の奇形や腎・泌尿器系の奇形が多い(PED.1122)　→　奇形を伴わない症例はtren-Dameshe症候群
身体：低身長
頭部：小頭症、知能発達遅延(知能障害)、小眼球症、斜視
皮膚：色素沈着、
心臓：心奇形
腎臓：腎の無形成、重複腎盂、馬蹄腎
内分泌：下垂体不全
血液：汎血球減少