ALAGILLE SYNDROME
FISH ANALYSIS

The Kleberg Cytogenetics Laboratory offers a fluorescence in situ hybridization (FISH)-based assay for identifying the microdeletion on the short arm of chromosome 20 associated with Alagille syndrome.

Clinical Features:

Alagille syndrome is an autosomal dominant disorder characterized by intrahepatic cholestasis and abnormalities of the heart, eye, vertebrae and kidney, as well as a characteristic facial appearance. There is a high rate of new mutation (50-60% of cases) and considerable phenotypic variability.

Reasons for Referral:

Patients with clinical features suggestive of Alagille syndrome may be tested for microdeletions of 20p12 by FISH. Since there is considerable variability in this syndrome, testing of first-degree relatives of an affected individual (FISH positive) may be warranted. Prenatal diagnosis may be performed if an affected family member has been studied in our laboratory and shown to have a deletion detectable by FISH. Please call regarding all prenatal samples.

Testing Methodology:

FISH is the application of fluorescently labeled DNA molecules to metaphase chromosomes and interphase nuclei for the detection of chromosome abnormalities and alterations. It is a rapid, reliable and direct approach for identifying patients with microdeletions or microduplications. FISH analysis for Alagille syndrome is performed on metaphase chromosomes. The absence of a hybridization signal indicates a deletion. Microdeletions of 20p12, including the JAG1 gene, may be detected in a small percentage of individuals with Alagille syndrome (5-7%). The majority of patients with Alagille syndrome will have mutations in the JAG1 gene that are not detectable by FISH. Therefore, if FISH is negative, further molecular testing may be indicated in patients with a clinical diagnosis of Alagille syndrome.

Specimen Requirements:

Whole blood in sodium heparin (green-top) tubes:
Newborn (< 3 months): Minimum 0.5 -2.0 CC
Adult/Child: Minimum 3.0 -5.0 CC

Shipping and Handling:

All tubes must be labeled with the patient's testname and date of birth, and a completed requisition form must accompany each sample. If the laboratory is billing the patient's insurance, please enclose a copy of the insurance card. Ship specimens for overnight delivery at ambient temperature. Please notify the laboratory of incoming samples.

Turnaround Time:

7-10 days

CPT Codes and Prices:

88230, 88271, 88273, 88291

References:

1. Li, et al. (1997) Nat. Genet. 16: 243-251.
2. Krantz, et al. (1997) Am. J. Med. Genet. 70: 80-86.
3. Krantz, et al. (1998) Am. J. Med. Genet. 62: 1361-1369.

Forms:

>> Cytogenetics Requisition
>> Prenatal Requisition

Test Code:

8458