Test Code SEP9Z SEPTIN9 Gene, Full Gene Analysis, Varies

Ordering Guidance

Targeted testing (also called site-specific or known variants testing) is available for variants identified in the SEPTIN9 gene. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Testing for SEPTIN9 gene as part of a customized panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

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.

Specimen Type: Whole blood

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

Forms

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Secondary ID

617714

Useful For

Establishing a molecular diagnosis for patients with hereditary neuralgic amyotrophy

Identifying variants within SEPTIN9 known to be associated with hereditary neuralgic amyotrophy, allowing for predictive testing of at-risk family members

Disease States

Hereditary neuralgic amyotrophy

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

SEPTIN9 Gene, Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder characterized by periods of severe pain involving the brachial plexus followed by muscle atrophy and weakness. These recurrent episodes can also be accompanied by decreased sensation and paresthesias. Individuals with this disease are generally symptom-free between pain attacks, though many patients experience lingering effects with repeated attacks. The pain episodes are frequently triggered by physical, emotional, or immunological stress. Less commonly, affected individuals can exhibit non-neurological features including short stature, skin folds, hypotelorism, and cleft palate.

Variants in the SEPTIN9 gene cause the clinical manifestations of HNA. SEPTIN9 is currently the only known gene associated with HNA, although approximately 15% of HNA families do not show linkage to this gene.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

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 SEPTIN9, as well as some other regions that have known disease-causing 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 deletion/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 (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in SEPTIN9.

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.(Unpublished Mayo method)

The reference transcript for SEPTIN9 gene is NM_006640.4. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Day(s) Performed