Interpretive Handbook

Test 61100 :
SEPT9 Gene, Mutation Screen

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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.


Mutations in the SEPT9 gene cause the clinical manifestations of HNA. There are 3 common mutations that have been reported in affected individuals: c.-134G->C, p.R88W, and p.S93F. Additionally, a common exonic duplication attributed to the founder effect has been identified in North American HNA families. Other private duplications of varying sizes have also been identified in affected individuals. SEPT9 is currently the only known gene associated with HNA, although approximately 15% of HNA families do not show linkage to this gene.

Useful For Suggests clinical disorders or settings where the test may be helpful

Confirmation of a diagnosis of hereditary neuralgic amyotrophy

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Some individuals who are a carrier or have a diagnosis of hereditary neuralgic amyotrophy may have a mutation that is not identified by this method (eg, mutations in other exons, deep intronic alterations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of hereditary neuralgic amyotrophy. For carrier testing, it is important to first document the presence of a SEPT9 gene mutation in an affected family member.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions for testing patients who have received a bone marrow transplant.  


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


In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Hannibal MC, Ruzzo EK, Miller LR, et al: SEPT9 gene sequencing analysis reveals recurrent mutations in hereditary neuralgic amyotrophy. Neurology 2009 May 19;72(20):1755-1759

2. Landsverk ML, Ruzzo EK, Mefford HC, et al: Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy. Hum Mol Genet 2009 Apr 1;18(7):1200-1208

3. Collie AM, Landsverk ML, Ruzzo E, et al: Non-recurrent SEPT9 duplications cause hereditary neuralgic amyotrophy. J Med Genet 2010 Sep;47(9):601-607