Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy

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ClinicalTrials.gov Identifier: NCT00001813

Recruitment Status : Recruiting

First Posted : November 4, 1999

Last Update Posted : June 28, 2022

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description

Brief Summary:

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....

Condition or disease
Cockayne Syndrome Skin Neoplasms Xeroderma Pigmentosum Trichothiodystrophy Genodermatosis

Detailed Description:

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.

Study Design

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Study Type :	Observational
Estimated Enrollment :	750 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
Actual Study Start Date :	May 10, 1999

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Trichothiodystrophy Cockayne syndrome Xeroderma pigmentosum

Genetic and Rare Diseases Information Center resources: Xeroderma Pigmentosum Cockayne Syndrome Trichothiodystrophy

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
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

Outcome Measures

Primary Outcome Measures :

Identify patients with genetic diseases [ Time Frame: Up to 3 days ]
Proportion of patients with three rare genetic diseases; xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD)and overlap syndromes

Secondary Outcome Measures :

Diagnosis confirmation [ Time Frame: 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
Tissue collection [ Time Frame: up to 3 days ]
obtain tissue (skin, blood, hair or buccal cells) from XP, CS, TTD, XP/TTD or overlap syndrome patients, their firstdegree relatives and healthy volunteers for establishment of cell cultures and for examination of DNA repair and genetic analysis
identify molecular defects [ Time Frame: up to 3 days ]
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
overall survival [ Time Frame: yearly ]
follow the clinical course of selected patients with XP, CS, TTD, XP/TTD or overlap syndromes

Eligibility Criteria

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Ages Eligible for Study:	42 Days and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

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.

Criteria

INCLUSION CRITERIA:
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
Healthy volunteers of age 1 year and above (including NIH employees) willing to donate blood, skin, buccal cells, or hair.
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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001813

Contacts

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Contact: Deborah E Tamura, R.N.	(240) 760-7355	dt220a@nih.gov
Contact: Kenneth H Kraemer, M.D.	(240) 760-6139	kraemerk@mail.nih.gov

Locations

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

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Principal Investigator:	Kenneth H Kraemer, M.D.	National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

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.

Boltshauser E, Yalcinkaya C, Wichmann W, Reutter F, Prader A, Valavanis A. MRI in Cockayne syndrome type I. Neuroradiology. 1989;31(3):276-7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00001813
Obsolete Identifiers:	NCT00004044
Other Study ID Numbers:	990099 99-C-0099
First Posted:	November 4, 1999 Key Record Dates
Last Update Posted:	June 28, 2022
Last Verified:	March 28, 2022

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):


Xeroderma Pigmentosum Trichothiodystrophy Cockayne Syndrome	Skin Cancer DNA Repair Natural History

Additional relevant MeSH terms:

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Skin Neoplasms Xeroderma Pigmentosum Cockayne Syndrome Ichthyosis Trichothiodystrophy Syndromes Syndrome Disease Pathologic Processes Congenital Abnormalities Neoplasms by Site Neoplasms Skin Diseases Precancerous Conditions Skin Abnormalities Skin Diseases, Genetic	Genetic Diseases, Inborn Photosensitivity Disorders Pigmentation Disorders DNA Repair-Deficiency Disorders Metabolic Diseases Infant, Newborn, Diseases Keratosis Dwarfism Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Abnormalities, Multiple

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