Hirschsprung Disease Genetic Study

NCT00478712 | Recruiting

• 1 other identifier: 17-01813
• Study Type: observational
• Target: 3,000
• Locations: 1 country
• Sites: 1

Brief Summary

Hirschsprung disease is a genetic condition caused by lack of nerve cells in varying lengths of the intestines. This study will investigate the complex genetic basis of the disease, which involves multiple interacting genetic factors.

Conditions

Hirschsprung Disease

Keywords

Hirschsprung

Outcome Measures

Primary Outcomes (3)

• Discovery and characterization of common genetic variation associated with Hirschsprung disease

  Genome-wide assays of common genetic variation will be assessed using single nucleotide polymorphism (SNP) arrays

  DNA is isolated up to 1 year after enrollment

• Discovery and characterization of copy number variants associated with Hirschsprung disease

  Copy number variation will be detected using next generation sequencing data and high resolution microarrays that allow for detection of copy number variants across the genome

  DNA is isolated up to 1 year after enrollment

• Discovery and characterization of rare genetic variation associated with Hirschsprung disease

  Exome sequencing will be used to detect rare variation across all genes in the genome

  DNA is isolated up to 1 year after enrollment

Secondary Outcomes (8)

• Correlation of genetic variants with location of transition zone in Hirschsprung disease

  Baseline pathology data is obtained up to 1 year after enrollment

• Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease

  Baseline clinical data is obtained up to 1 year after enrollment

• Characterization of Hirschsprung disease that co-occurs with a known chromosomal disorder

  Baseline clinical data is obtained up to 1 year after enrollment

• Characterization of Hirschsprung disease that co-occurs with a known single gene syndrome

  Baseline clinical data is obtained up to 1 year after enrollment

• Characterization of Hirschsprung disease that co-occurs with other congenital anomalies without a known diagnosis

  Baseline clinical data is obtained up to 1 year after enrollment

Study Arms (1)

Families with Hirschsprung Disease

Individuals with Hirschsprung disease and their affected and unaffected relatives.

Other: Identification of genetic causes of Hirschsprung Disease

Interventions

Identification of genetic causes of Hirschsprung Disease OTHER

Blood, saliva, or DNA samples are requested from all study participants. The blood or saliva samples are used to isolate DNA in all participants. Blood samples are also used to establish cell lines in some participants.

Families with Hirschsprung Disease

Eligibility Criteria

• Age: 1 Week - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes individuals with Hirschsprung disease and their family members.

You may qualify if:

• \- Individuals with Hirschsprung disease and their first degree relatives (any segment length of disease, with or without other congenital anomalies or health problems, single or multiple affected individuals in family)

You may not qualify if:

• Unable or unwilling to provide sample for genetic studies
• Individual, parent, or guardian unable to comprehend and provide informed consent

Sponsors & Collaborators

• NYU Langone Health: lead
• New York University: collaborator

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

RECRUITING

Related Publications (7)

• Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990 Mar;46(3):568-80.

  PMID: 2309705 BACKGROUND

• Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED, Chakravarti A. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature. 2005 Apr 14;434(7035):857-63. doi: 10.1038/nature03467.

  PMID: 15829955 RESULT

• Gabriel SB, Salomon R, Pelet A, Angrist M, Amiel J, Fornage M, Attie-Bitach T, Olson JM, Hofstra R, Buys C, Steffann J, Munnich A, Lyonnet S, Chakravarti A. Segregation at three loci explains familial and population risk in Hirschsprung disease. Nat Genet. 2002 May;31(1):89-93. doi: 10.1038/ng868. Epub 2002 Apr 15.

  PMID: 11953745 RESULT

• Arnold S, Pelet A, Amiel J, Borrego S, Hofstra R, Tam P, Ceccherini I, Lyonnet S, Sherman S, Chakravarti A. Interaction between a chromosome 10 RET enhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association. Hum Mutat. 2009 May;30(5):771-5. doi: 10.1002/humu.20944.

  PMID: 19306335 RESULT

• Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, Amiel J, Burzynski G, Fernandez RM, Hao L, Kashuk C, West K, Miao X, Tam PK, Griseri P, Ceccherini I, Pelet A, Jannot AS, de Pontual L, Henrion-Caude A, Lyonnet S, Verheij JB, Hofstra RM, Antinolo G, Borrego S, McCallion AS, Chakravarti A. Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet. 2010 Jul 9;87(1):60-74. doi: 10.1016/j.ajhg.2010.06.007.

  PMID: 20598273 RESULT

• Kapoor A, Jiang Q, Chatterjee S, Chakraborty P, Sosa MX, Berrios C, Chakravarti A. Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms. Hum Mol Genet. 2015 May 15;24(10):2997-3003. doi: 10.1093/hmg/ddv051. Epub 2015 Feb 9.

  PMID: 25666438 RESULT

• Chatterjee S, Kapoor A, Akiyama JA, Auer DR, Lee D, Gabriel S, Berrios C, Pennacchio LA, Chakravarti A. Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease. Cell. 2016 Oct 6;167(2):355-368.e10. doi: 10.1016/j.cell.2016.09.005. Epub 2016 Sep 29.

  PMID: 27693352 RESULT

Related Links

• Chakravarti, Johns Hopkins Medical Institution (JHMI) Faculty Biography Page

Biospecimen

Retention: SAMPLES WITH DNA

Study volunteers are asked to provide blood or cheek swab/saliva samples. DNA is extracted from the samples for use in the study.

MeSH Terms

Conditions

Hirschsprung Disease

Condition Hierarchy (Ancestors)

Digestive System Abnormalities; Digestive System Diseases; Megacolon; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Aravinda Chakravarti, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jenna Pucel, MS, CGC

CONTACT

212-263-8069; jenna.pucel@nyulangone.org

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2007
• First Posted: May 25, 2007
• Study Start: January 1, 2001
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 30, 2025

Record last verified: 2025-07

Locations

US (1)