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

NCT00001642 | Completed

• 2 other identifiers: 97012297-HG-0122
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

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.

Conditions

Alagille Syndrome

Keywords

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Human Genome Research Institute (NHGRI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 803282 BACKGROUND

• 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.

  PMID: 3806290 BACKGROUND

• 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.

  PMID: 9207787 BACKGROUND

MeSH Terms

Conditions

Alagille Syndrome; Chromosome Deletion

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Monosomy; Aneuploidy; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 6, 2000
• First Posted: December 10, 2002
• Study Start: May 1, 1997
• Study Completion: March 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-05

Locations

US (1)