Test Id : ALAGP

Targeted testing for familial variants (also called site-specific or known mutations/variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Specimen preferred to arrive within 96 hours of collection.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)
• Hereditary Renal Genetic Testing Patient Information
• Targeted Genes and Methodology Details for Alagille Syndrome Gene Panel

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Hereditary Renal Genetic Testing Patient Information (T918)

3. If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.

1 mL

Providing a genetic evaluation for patients with a personal or family history suggestive of Alagille syndrome

Establishing a diagnosis of Alagille syndrome

This test utilizes next-generation sequencing to detect single nucleotide, small deletion-insertion, and copy number variants in two genes (JAG1, NOTCH2) associated with Alagille syndrome. See Targeted Genes and Methodology Details for Alagille Syndrome Gene Panel and Method Description for additional details.

Alagille syndrome (ALGS) is a multisystemic genetic condition with a wide spectrum of clinical variability. Characteristic features of ALGS include bile duct paucity, cholestasis, congenital heart defects, butterfly vertebrae, eye findings, and facial features including a broad forehead, deeply set eyes, and a small, pointed chin.(1) Approximately 40% of individuals also have kidney disease. The kidney features may include structural abnormalities (eg, small hyperechoic kidney, kidney cysts, or ureteropelvic obstruction) as well as kidney dysfunction, such as renal tubular acidosis.

Disease-causing variants in the JAG1 gene account for approximately 94% to 97% of ALGS, while disease-causing NOTCH2 gene variants account for approximately 1% to 3% of cases.(1,2) A small percentage of individuals with a clinical diagnosis of ALGS do not have an identified disease-causing variant in either JAG1 or NOTCH2.

The severity of ALGS is highly variable among individuals, ranging from mild and subclinical, to severe heart or liver disease requiring transplantation. ALGS is inherited in an autosomal dominant manner. Approximately 30% to 50% of individuals inherit ALGS from an affected parent, while about 50% to 70% of cases are de novo. Parental somatic mosaicism and germline mosaicism have been reported.

An interpretive report will be provided.

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(3) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Alagille Syndrome Gene Panel for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

1. Spinner NB, Gilbert MA, Loomes KM, Krantz ID: Alagille syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 12, 2019. Accessed June 7, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1273/

2. Turnpenny P, Ellard S: Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012 Mar;20(3):251-257

3. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

81407

81479

81479 (if appropriate for government payers)