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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00001813

Collaborator

(none)

750

Enrollment

Location

Study Details

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	Intervention/Treatment	Phase
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

Study Type:

Observational

Anticipated 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

Arms and Interventions

Arm	Intervention/Treatment
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 [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 [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 [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 [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 [yearly]
follow the clinical course of selected patients with XP, CS, TTD, XP/TTD or overlap syndromes

Eligibility Criteria

Criteria

Ages Eligible for Study:

42 Days and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.