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

Overview

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.

Study Type

• Study Type: Observational
• Study Design
  • Time Perspective: Prospective

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.

Arms, Groups and Cohorts

• 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

Clinical Trial Outcome Measures

Primary 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 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 first-degree 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 6 Weeks

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • National Cancer Institute (NCI)
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Kenneth H Kraemer, M.D., Principal Investigator, National Cancer Institute (NCI)
• Overall Contact(s)
  • Deborah E Tamura, R.N., (240) 760-7355, dt220a@nih.gov

References

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.