Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Telomere Repair Gene Mutation in Inflammatory Bowel Disease

Summary: This study will evaluate and compare the genes of the telomere repair complex in healthy control subjects, patients with blood diseases, and patients with inflammatory bowel disease to identify what, if any, changes are associated specifically with inflammatory bowel disease.
  Patients between 2 and 80 years of age with ulcerative colitis or regional enteritis may be eligible for this study. Participants are recruited from the practice of Dr. Stuart Danovitch, Washington, D.C.
  Researchers have established that minor differences in a specific set of genes called the telomere repair complex are related to immune-mediated diseases of the bone marrow. NIH researchers are now interested in whether inflammatory bowel disease and other autoimmune diseases show a similar pattern of genetic differences.
  Participants provide a cell sample for evaluation of the telomere repair complex. The sample is collected via buccal swab, a gentle scraping of the inside of the cheek, and stored for use in research.

Detailed description: We have identified inherited mutations in genes of the telomere repair complex in patients with acquired aplastic anemia. These mutations diminish the ability of cells to repair the ends of chromosomes, called telomeres, which normally shorten with each cell division. Mutations in TERC, the gene which encodes for the RNA template of the complex; in TERT, the gene for the enzyme in the complex, and also in the Schwachman-Bodian-Diamond syndrome gene (SBDS), which we believe to be associated with telomere repair, lead to reduced telomerase activity, diminished numbers of hematopoietic cells in the bone marrow, and presumably also a deficiency in the ability of cells to respond to immunological attack and destruction of the hematopoietic system.
  This laboratory research protocol will allow us to evaluate whether similar gene mutations might underlie other autoimmune diseases, here specifically, inflammatory bowel disease, which share broad pathophysiologic features with immune-mediated aplastic anemia. We will directly assess by DNA sequencing suspect genes (TERC, TERT, SBDS, DNA helicases and others) in buccal mucosal samples obtained from patients with inflammatory bowel disease (IBD). Analyses from large numbers of controls have defined polymorphisms for these genes. IBD samples will allow us to determine whether mutations in these genes are more prevalent in this patient population and to test the hypotheses that telomere repair defects underlie human autoimmunity, or that these genes are specifically involved in hematology as risks factors for bone marrow failure.

Eligibility: -  INCLUSION CRITERIA:
  Diagnosis of ulcerative colitis or regional enteritis
  For adults:
  Ability to comprehend the investigational nature of the study and provide informed consent. Or
  For minors: Written informed consent from one parent or guardian and informed assent. The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.
  Age greater than 2 but less or equal to 80 years old
  EXCLUSION CRITERIA:
  All subjects not fulfilling the inclusion criteria will be considered ineligible.

Relevance to patient case: not relevant