Undersøgelse af kliniske og laboratoriemæssige abnormiteter hos patienter med defekt DNA-reparation: Xeroderma Pigmentosum, Cockayne Syndrom eller Trichothiodystrophy
Four rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, XP/CS, CS, or TTD and follow their clinical course. We will obtain tissue (skin, blood, hair, buccal swabs) for laboratory examination of DNA repair and for genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.
Studieoversigt
Status
Detaljeret beskrivelse
Three rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. We plan to perform careful clinical examination of selected patients with XP, CS, TTD, or overlap syndromes to follow their clinical course. We will obtain tissue (skin, blood, hair, or buccal cells) for laboratory examination of DNA repair and for histologic, protein, biochemical, and genetic analysis. We hope to be able to correlate these laboratory abnormalities with the clinical features to better understand the mechanism of cancer prevention by DNA repair. Patients will be offered counseling and education for cancer control.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
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Maryland
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Bethesda, Maryland, Forenede Stater, 20892
- National Institutes of Health Clinical Center
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Prøveudtagningsmetode
Studiebefolkning
Patients will be sought by contacting professional organizations (such as the American Academy of Dermatology-XP Task Force), lay support groups (such as the XP Society and the Share and Care CS Support Network) or by direct referral. Healthy volunteers or NIH staff will be recruited through the Program for Healthy Volunteers (CRVP@mail.cc.nih.gov), through the Patient Recruitment and Public Liaison Office (prpl@mail.cc.nih.gov), or as a self-referral through the clinicaltrials.gov web site (http://clinicaltrials.gov). Healthy volunteers may also be approached by a member of the LCBG, NCI regarding interest in participating on this protocol.
Beskrivelse
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INCLUSION CRITERIA:
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Subjects age 6 weeks and above:
- with clinical and/or laboratory documentation of typical features or suggestive clinical features of XP, CS, TTD, or overlap syndromes or
- that are first degree relatives or other family members of participants with XP, CS, TTD, or overlap syndromes
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Healthy volunteers of age 1 year and above (including NIH employees) willing to donate blood, skin, buccal cells, or hair.
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Patients or legally authorized representatives must provide informed consent.
EXCLUSION CRITERIA:
-Inability or unwillingness to provide tissue (skin, blood, buccal cells or hair) for laboratory studies.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Observationsmodeller: CASE_CONTROL
- Tidsperspektiver: PROSPECTIVE
Kohorter og interventioner
Gruppe / kohorte |
|---|
|
1
Subjects with clinical and/or laboratory documentation of typical features or suggestiveclinical features of XP, CS, TTD, or overlap syndromes |
|
2
Family members of patients with XP, CS, TTD, or overlap syndromes |
|
3
Healthy volunteers |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Identify patients with genetic diseases
Tidsramme: Up to 3 days
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Proportion of patients with three rare genetic diseases; xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD)and overlap syndromes |
Up to 3 days
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Diagnosis confirmation
Tidsramme: up to 3 days
|
-To confirm suspected cases of XP, CS, TTD, XP/TTD or overlap syndrome patients by review of clinical records, by clinical examination and by laboratory testing -To document presence (or absence) of cancers (skin, eye, tongue, or internal) in XP, XP/CS, CS, TTD, XP/TTD and other overlap syndrome patients-To document atypical clinical features or unusual environmental exposures of patients with XP, XP/CS, CS, TTD, XP/TTD and otheroverlap syndromes |
up to 3 days
|
|
Tissue collection
Tidsramme: up to 3 days
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obtain tissue (skin, blood, hair or buccal cells) from XP, CS, TTD, XP/TTD or overlap syndrome patients, their first-degree relatives and healthy volunteers for establishment of cell cultures and for examination of DNA repair and genetic analysis |
up to 3 days
|
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identify molecular defects
Tidsramme: up to 3 days
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identify molecular defects in the DNA repair or other genes in cells from patients with XP, CS, TTD, XP/TTD or overlap syndromes and toattempt to correlate the defects with the clinical features |
up to 3 days
|
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overall survival
Tidsramme: yearly
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follow the clinical course of selected patients with XP, CS, TTD, XP/TTD or overlap syndromes |
yearly
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Michael R Sargen, M.D., National Cancer Institute (NCI)
Publikationer og nyttige links
Generelle publikationer
- Barrett SF, Robbins JH, Tarone RE, Kraemer KH. Evidence for defective repair of cyclobutane pyrimidine dimers with normal repair of other DNA photoproducts in a transcriptionally active gene transfected into Cockayne syndrome cells. Mutat Res. 1991 Nov;255(3):281-91. doi: 10.1016/0921-8777(91)90032-k.
- Boltshauser E, Yalcinkaya C, Wichmann W, Reutter F, Prader A, Valavanis A. MRI in Cockayne syndrome type I. Neuroradiology. 1989;31(3):276-7. doi: 10.1007/BF00344359.
- Merideth M, Tamura D, Angra D, Khan SG, Ferrell J, Goldstein AM, DiGiovanna JJ, Kraemer KH. Reproductive Health in Xeroderma Pigmentosum: Features of Premature Aging. Obstet Gynecol. 2019 Oct;134(4):814-819. doi: 10.1097/AOG.0000000000003490.
- Atkinson EC, Thiara D, Tamura D, DiGiovanna JJ, Kraemer KH, Hadigan C. Growth and nutrition in children with trichothiodystrophy. J Pediatr Gastroenterol Nutr. 2014 Oct;59(4):458-64. doi: 10.1097/MPG.0000000000000458.
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Anslået)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Knoglesygdomme
- Muskuloskeletale sygdomme
- Sygdomme i nervesystemet
- Neoplasmer efter sted
- Neoplasmer
- Genetiske sygdomme, medfødte
- Metaboliske sygdomme
- Neurodegenerative sygdomme
- Hudsygdomme
- Forstadier til kræft
- Medfødte abnormiteter
- Abnormiteter, multiple
- Heredodegenerative lidelser, nervesystem
- Pigmenteringsforstyrrelser
- Hudabnormiteter
- DNA-reparation-mangellidelser
- Knoglesygdomme, udviklingsmæssige
- Lysfølsomhedsforstyrrelser
- Dværgvækst
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Ernæringsmæssige og metaboliske sygdomme
- Hud- og bindevævssygdomme
- Neoplasmer i huden
- Hudsygdomme, genetisk
- Xeroderma Pigmentosum
- Cockayne syndrom
- Trichothiodystrophy syndromer
Andre undersøgelses-id-numre
- 990099
- 99-C-0099
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
IPD-delingstidsramme
-Clinical data available during the study and indefinitely.@@@@@@-Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active
IPD-delingsadgangskriterier
-Clinical data will be made available and with the permission of the study PI.@@@@@@-Genomic data are made available via dbGaP through requests to the data custodians.
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
- ICF
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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