Positional Cloning of the Gene(s) Responsible for Alagille Syndrome - Full Text View

Study Description

Brief Summary:

The goal of the project is to identify and clone the gene(s) responsible for the Alagille Syndrome (AGS) by a positional cloning approach. The first step towards this goal is to define the smallest genomic candidate region for AGS at 20p12 and to begin to identify genes within this region which are, by definition, candidate genes for the disease. In a collaborative effort with clinician-investigators studying the Alagille syndrome, metaphase chromosomes and genomic DNA from affected individuals will be studied for subchromosomal deletions and for mutations in the candidate genes. Characterization of genes involved in Alagille syndrome could provide important insight into the pathophysiology of the disease, the development of normal liver and treatment of this disease. Recently, we and others found that mutations in Jagged1, a Notch1 receptor are responsible for Alagille Syndrome.

Condition or disease
Alagille Syndrome

Detailed Description:

The goal of the project is to identify and clone the gene(s) responsible for the Alagille Syndrome (AGS) by a positional cloning approach. The first step towards this goal is to define the smallest genomic candidate region for AGS at 20p12 and to begin to identify genes within this region which are, by definition, candidate genes for the disease. In a collaborative effort with clinician-investigators studying the Alagille syndrome, metaphase chromosomes and genomic DNA from affected individuals will be studied for subchromosomal deletions and for mutations in the candidate genes. Characterization of genes involved in Alagille syndrome could provide important insight into the pathophysiology of the disease, the development of normal liver and treatment of this disease.

Study Design


Study Type :	Observational
Enrollment :	225 participants
Official Title:	Positional Cloning of the Gene(s) Responsible for Alagille Syndrome
Study Start Date :	May 1997
Study Completion Date :	March 2000

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Alagille syndrome

MedlinePlus related topics: Genes and Gene Therapy

Genetic and Rare Diseases Information Center resources: Alagille Syndrome

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

All enrolled affected subjects, whose samples will be analyzed in this study, must meet the criteria for the clinical diagnosis of Alagille Syndrome (Syndromic Bile Duct Paucity) which include liver biopsy findings consistent with Alagille Syndrome and at least 3 of the 5 primary clinical criteria: cholestasis, characteristic face, posterior embryotoxon, "butterfly" vertebrae and cardiac findings.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001642

Locations


United States, Maryland
National Human Genome Research Institute (NHGRI)
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Human Genome Research Institute (NHGRI)

More Information

Publications:

Alagille D, Odièvre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. 1975 Jan;86(1):63-71.

Alagille D, Estrada A, Hadchouel M, Gautier M, Odièvre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987 Feb;110(2):195-200.

Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, Piccoli DA, Meltzer PS, Spinner NB, Collins FS, Chandrasekharappa SC. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997 Jul;16(3):235-42.


ClinicalTrials.gov Identifier:	NCT00001642 History of Changes
Other Study ID Numbers:	970122 97-HG-0122
First Posted:	December 10, 2002 Key Record Dates
Last Update Posted:	March 4, 2008
Last Verified:	May 1999

Keywords provided by National Institutes of Health Clinical Center (CC):


Chromosomal Deletion Mutations Paucity of Bile Ducts Physical Map	Transcript Identification Alagille Syndrome Syndromic Bile Duct Paucity

Additional relevant MeSH terms:


Syndrome Alagille Syndrome Disease Pathologic Processes Cholestasis, Intrahepatic Cholestasis Bile Duct Diseases Biliary Tract Diseases	Digestive System Diseases Liver Diseases Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases Abnormalities, Multiple Congenital Abnormalities Genetic Diseases, Inborn