Clinical Research Studies

Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Ondine’s curse (Congenital Central Hypoventilation syndrome (CCHS)). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described. The goal of our research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families by whole genome mapping and sequencing studies. Specifically, we intend to ascertain the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Further, we will collect clinical information and investigate possible genotype – phenotype correlations. The subject population consists of individuals diagnosed with HSCR and their unaffected relatives. Individuals/families are ascertained through support groups, web-based listings of research studies and genetic testing services, an educational Hirschsprung disease website, and referrals from genetic counselors and physicians. Blood, or tissue, samples are requested from affected individuals and their unaffected relatives. The blood/tissue samples received are anonymized; samples are coded with a family and individual number. The identity of the study participants will be known only to Dr. Chakravarti, the study coordinator, and the post-doctoral fellow(s) working directly on the project. DNA, lymphocytes, and lymphoblastoid cell lines may be prepared from the blood samples for future use. Molecular analysis using markers and sequencing, and statistical analysis of these data, will be used to identify regions of human chromosomes where putative HSCR disease genes may be located. In addition, we will analyze the DNA sequence of known and/or suspected HSCR genes or the whole genome in individual patients and their family members, in search of causative HSCR susceptibility variants. Study subjects will not directly benefit from participation; the purpose of the study is to better understand the etiology of HSCR, leading to improved detection, treatment, and management. Results will not be disclosed to participants nor their health care providers, unless medically relevant. Our laboratory is not CLIA approved and thus, analysis is completed for research purposes only. However, in the event that we identify a clinically significant and actionable result that may affect the participant’s future health, such as a RET mutation that confers a risk for multiple endocrine neoplasia, type 2A (MEN2A), the individual may be contacted with options for receiving the potential result after submitting a new blood sample for CLIA confirmation.