Positional Cloning of the Gene(s) Responsible for Alagille Syndrome

NCT ID: NCT00001642

Last Updated: 2008-03-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 225 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1997-05-31
• Study Completion Date: 2000-03-31

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.

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.

Conditions

Alagille Syndrome

Eligibility Criteria

Inclusion 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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: lead

Locations

National Human Genome Research Institute (NHGRI)

Bethesda, Maryland, United States

Countries

United States

References

Alagille D, Odievre 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. doi: 10.1016/s0022-3476(75)80706-2.

Reference Type: BACKGROUND

PMID: 803282 (View on PubMed)

Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre 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. doi: 10.1016/s0022-3476(87)80153-1.

Reference Type: BACKGROUND

PMID: 3806290 (View on PubMed)

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. doi: 10.1038/ng0797-235.

Reference Type: BACKGROUND

PMID: 9207787 (View on PubMed)

Other Identifiers

97-HG-0122

Identifier Type: -

Identifier Source: secondary_id

970122

Identifier Type: -

Identifier Source: org_study_id