Esame delle anomalie cliniche e di laboratorio nei pazienti con riparazione difettosa del DNA: xeroderma pigmentoso, sindrome di Cockayne o tricotiodistrofia
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....
Panoramica dello studio
Stato
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Contatti e Sedi
Luoghi di studio
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Maryland
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Bethesda, Maryland, Stati Uniti, 20892
- National Institutes of Health Clinical Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Metodo di campionamento
Popolazione di studio
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.
Descrizione
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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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Modelli osservazionali: CASE_CONTROL
- Prospettive temporali: PROSPECTIVE
Coorti e interventi
Gruppo / Coorte |
|---|
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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 |
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3
Healthy volunteers |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Identify patients with genetic diseases
Lasso di tempo: 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
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Diagnosis confirmation
Lasso di tempo: up to 3 days
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-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
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Tissue collection
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Michael R Sargen, M.D., National Cancer Institute (NCI)
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
Collegamenti utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stimato)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie ossee
- Malattie muscoloscheletriche
- Malattie del sistema nervoso
- Neoplasie per sede
- Neoplasie
- Malattie genetiche, congenite
- Malattie metaboliche
- Malattie Neurodegenerative
- Malattie della pelle
- Condizioni precancerose
- Anomalie congenite
- Anomalie multiple
- Malattie Eredodegenerative, Sistema Nervoso
- Disturbi della pigmentazione
- Anomalie della pelle
- Disturbi da carenza di riparazione del DNA
- Malattie ossee, dello sviluppo
- Disturbi da fotosensibilità
- Nanismo
- Malattie e anomalie congenite, ereditarie e neonatali
- Malattie nutrizionali e metaboliche
- Malattie della pelle e del tessuto connettivo
- Neoplasie cutanee
- Malattie della pelle, genetiche
- Xeroderma pigmentoso
- Sindrome di Cockayne
- Sindromi da tricotiodistrofia
Altri numeri di identificazione dello studio
- 990099
- 99-C-0099
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
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.
Periodo di condivisione IPD
-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
Criteri di accesso alla condivisione IPD
-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.
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- LINFA
- ICF
Informazioni su farmaci e dispositivi, documenti di studio
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Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
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