Alagille Syndrome (AGS) is a multisystem disorder with an estimated incidence of at least 1/70,000. Diagnostic criteria require three of the following five major features: cholestasis due to bile duct paucity, cardiac defect (often pulmonic stenosis or tetralogy of Fallot), anterior chamber defects of the eye (especially posterior embryotoxon), butterfly vertebrae or other skeletal abnormalities, and characteristic facial features. Less frequent findings include functional and structural defects of the kidneys, pancreatic insufficiency, and vascular abnormalities. Most patients are diagnosed in infancy. Mortality is 10% with early deaths due to cardiac or severe liver disease and late mortality from vascular accidents.

Alagille Syndrome is caused by heterozygous dominant mutations in the JAG1 gene (also called JAGGED1, OMIM #601920). Penetrance is high, but diagnosis may be complicated by the large proportion of de novo mutations (50-70%) and highly variable clinical expression even within the same family. Severity ranges from multisystem involvement with critical liver or cardiac disease, to isolated cardiac defects, to subclinical vertebral or facial changes. Therefore, evaluation of first degree relatives of a proband should be considered. DNA testing helps diagnose this variable condition. Approximately 95% of AGS patients have mutations detectable by the Ambry Test through sequence analysis of JAG1 (~88%) and further testing for gross gene deletions and duplications (~7%). The NOTCH2 gene, not analyzed by the Ambry Test, causes less than 1% of AGS.

The Alagille AMPLIFIED Test is full gene sequence analysis of the JAG1 gene with reflex to deletion/duplication analysis if no mutation is found by sequencing. Results are reported 21-28 days after testing is initiated.

For patients who have previously had JAG1 sequencing with negative results, testing for only deletions and duplications is available. These results are reported 7-14 days after testing is initiated.

The following CPT Codes for the Ambry Test reflects Ambry Genetics’ interpretation of CPT coding requirements based on AMA guidelines:

Ambry Test: Alagille AMPLIFIED
83891, 83894, 83898, 83900, 83901, 83904, 83909, 83912

Ambry Test: Alagille Del/Dup
83891, 83894, 83900, 83901, 83909, 83912

CPT codes are provided only as a guide to assist you in billing. CPT coding is the sole responsibility of the billing party.

Disclaimer:

This test was developed and its performance characteristics were determined by Ambry Genetics Corporation. The laboratory is regulated under the Clinical Laboratory Improvement Amendments 2003 as qualified to perform non-waived testing. The Ambry Test: Alagille AMPLIFIED analyzes the following types of mutations: nucleotide substitutions, small deletions, small insertions, small indels, gross insertions, and gross deletions. It is not intended to analyze the following types of mutations: gross rearrangements, deep intronic variations, and other unknown abnormalities. The pattern of mutation types varies with the gene tested and the Ambry Test detects a high but variable percentage of known and unknown mutants of the classes stated. A negative result from the analysis cannot rule out the possibility that the tested individual carries a rare unexamined mutation or mutation in the undetectable group. The Ambry Test: Alagille AMPLIFIED is designed and validated to be capable of detecting about ~99% of described JAG1 mutations (considering ~1% to be the other types of mutations). These mutations are detected in ~95% of affected patients. Alagille Syndrome is a complex clinical disorder, which in most cases is due to alterations in the JAG1 gene generally detected by the Ambry Test: Alagille AMPLIFIED except as noted above. Mutations in other genes, e.g. NOTCH2, or JAG1 regions not tested by the Ambry Test: Alagille AMPLIFIED can also give rise to clinical conditions similar to Alagille Syndrome. Although molecular tests are highly accurate, rare diagnostic errors may occur. Possible diagnostic errors include sample mix-up, erroneous paternity identification, technical errors, clerical errors, and genotyping errors. Genotyping errors can result from trace contamination of PCR reactions, from maternal cell contamination in fetal samples, from rare genetic variants, which interfere with analysis, or from other sources. This report does not represent medical advice. Any questions, suggestions, or concerns regarding interpretation of results should be forwarded to a genetic counselor, medical geneticist, or physician skilled in interpretation of the relevant medical literature. References are available upon request.