Diagnostic Test Directory

Molecular Genetics Laboratory

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Alagille Syndrome (JAG1 Sequence and Deletion Analysis)

  • LIS Mnemonic: MBJAG1FS

    Collect

    Collect whole blood in a purple top (EDTA) tube. May send extracted DNA instead.

    Volume Required

    5 ml whole blood or 9 ug of DNA

    Minimum Required

    3 ml

    Transport

    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.

    Stability

    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm

Reported

4-6 weeks

CPT

81407, 81406

Disease Information

Clinical Features:

Alagille syndrome(AGS) is a multisystem disorder characterized by the histologic finding of bile duct paucity on liver biopsy, cholestasis, cardiac defects (stenosis of pulmonary artery), butterfly vertebrae and ophthalmologic abnormalities (posterior embryotoxon). Characteristic facial features include a prominent forehead, deep set eyes with mild hypertelorism, pointed chin, and saddle or straight nose with a bulbous tip. Renal, pancreatic and central nervous system abnormalities are also observed in some patients. The clinical features are variable even within the same family.

Molecular Genetics:

Mutations in the JAG1 gene are associated with the majority of cases of AGS. JAG1 is located on chromosome 20p12 and it encodes a highly conserved cell surface protein that is part of the Notch signaling pathway thought to regulate cell fate decisions in many cell types. The JAG1 protein acts as a ligand for the Notch transmembrane receptors.

Test Methods:

We offer DNA sequence analysis and deletion/duplication testing of the entire coding region of the JAG1 gene. These tests can be ordered as a panel or individually. PCR amplification and sequence analysis is performed on the coding exon including splice junctions. The patient’s gene sequence is compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay. Large deletions and duplications will be detected using multiplex ligation-dependent probe amplification assay (MLPA).

Detection Rate:

Sequence analysis of the JAG1 detects point mutations in 89% of patients with a clinical diagnosis of AGS (Crosnier et al. 1999, Krantz et al. 1998, Spinner et al. 2001, Warthen et al. 2006). Large deletions and microdeletions of 20p12 involving the JAG1 have been detected in an additional 7% of patients. Fewer than 1% of patients have a mutation in the NOTCH2 gene. About 30-50% of individuals with AGS have an affected parent. In the remaining 50-70% of patients, the mutations are de novo.

Related Tests:

Known mutation analysis is available to family members for mutations previously identified by sequence analysis.

Results:

Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.

Utility:

The clinical utility of the assay is to support a clinical diagnosis of the disease, facilitate genetic counseling, and assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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215-590-5221