Genetic Mosaicism in Hirschsprung's Disease
Hirschsprung's disease is a complex genetic disorder. The etiology of this disease is not completely understood. It is characterized by the absence of ganglia (nerve cells) in de distal colon. This impairs bowel relaxation which can lead to bowel disfunction, toxic megacolon, ileus and enterocolitis. So far, several genes have been identified that play a role in Hirschsprung's disease. The precise mechanisms however, remain unclear. This study wants to identify new mutations and hopefully clarify more about the etiology of the disease.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Genetics of Hirschsprung's Disease - Can Genetic Mosaicism Due to Early Somatic Mutations, Explain Disease Development?|
- New somatic mutation [ Time Frame: During surgery (coolection); after inclusion of approx. 25 patients (preliminairy analysis); final analysis after end of the study (approx. 3 years from first inclusion) ] [ Designated as safety issue: No ]Primary outcome measure of this study is to identify new (previously unknown) somatic mutations as a cause for the development of Hirschsprung's disease. Tissue to find these mutations will be gathered during surgery for all patients (see protocol). When sufficient samples are collected (est 25 samples) a first comparative analysis for new somatic mutations will be performed. After the end of the study a final analysis for new somatic mutation will be performed.
- Correlation disease type [ Time Frame: At the end of the study (approximately 3 years after inclusion of first patient) ] [ Designated as safety issue: No ]Secondary outcome measure is to assess if any of the found mutations can be correlated with the type of Hirschsprung's disease (i.e. long-segment, short segment). This will be done after all patients DNA is analysed for somatic mutations after closure of the study.
Biospecimen Retention: Samples With DNA
Blood samples, skin tissue, colon tissue
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|Contact: Rhiana Garritsen-Farid, MDfirstname.lastname@example.org|
|UMC St Radboud||Recruiting|
|Nijmegen, Gelderland, Netherlands, 6525GA|
|Contact: Ivo Blaauw, MD, PhD +31243611111 email@example.com|
|Principal Investigator: Ivo Blaauw, MD|
|Erasmus Medical Center - Sophia||Recruiting|
|Rotterdam, Zuid-Holland, Netherlands, 3015GJ|
|Contact: Rhiana Garritsen-Farid, MD +31107044473 firstname.lastname@example.org|
|Principal Investigator: Rhiana Garritsen-Farid, MD|
|Principal Investigator:||Rhiana Garritsen, MD||Erasmus MC - Sophia|