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

Skin Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00001813
• Other study ID #: 990099
• Secondary ID: 99-C-0099
• Status: Active, not recruiting
• Start date: May 10, 1999

Study information

• Verified date: December 26, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00004044

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 698
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Cockayne Syndrome
• Genodermatosis
• Ichthyosis
• Skin Neoplasms
• Syndrome
• Xeroderma Pigmentosum

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identify patients with genetic diseases	Proportion of patients with three rare genetic diseases; xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD)and overlap syndromes	Up to 3 days
Secondary	Diagnosis confirmation	-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
Secondary	Tissue collection	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
Secondary	identify molecular defects	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
Secondary	overall survival	follow the clinical course of selected patients with XP, CS, TTD, XP/TTD or overlap syndromes	yearly

External Links

•   NIH Clinical Center Detailed Web Page