Interpretive Handbook

Test 61811 :
C9orf72 Hexanucleotide Repeat, Molecular Analysis

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

Frontotemporal dementia (FTD) is a presenile dementia that affects the frontal and temporal lobes of the brain. Clinical presentation is variable and includes progressive changes in behavior and personality and language disturbances. Affected individuals may also exhibit extrapyramidal signs.


Amyotrophic lateral sclerosis (ALS) is a progressive neurologic disease affecting the upper and lower motor neurons. The disease is characterized by progressive spasticity, muscle wasting, and paralysis, typically leading to death from respiratory failure.


ALS and FTD are now thought to represent an overlapping spectrum of disease. Recent literature has found that approximately 40% of familial ALS and FTD cases have a large hexanucleotide repeat (GGGGCC) expansion in a noncoding region of C9orf72.

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

Molecular confirmation of clinically suspected cases of c9frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS), FTD, or ALS


Presymptomatic testing for individuals with a family history of c9FTD/ALS and a documented expansion in the C9orf72 gene

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

For predictive testing, it is important to first document the presence of the hexanucleotide repeat amplification in the C9orf72 gene in an affected family member to confirm that molecular expansion is the underlying mechanism of disease in the family.


We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.


Predictive testing of an asymptomatic child is not recommended.


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.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

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.

Normal alleles: <20 GGGGCC repeats

Intermediate alleles: 20-29 GGGGCC repeats

Penetrance: >29* GGGGCC repeats


*Alleles greater than 30 repeats are outside the reportable range for this assay and are detected using the companion Southern blot assay. There is not enough information at this time to determine if 30 repeats is the cutoff for pathogenicity.


An interpretive report will be provided.

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

1. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al: Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011;72(2):245-256

2. Gijselinck I, Van Langenhove T, van der Zee J, et al: A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study. Lancet Neurol 2012;11(1):54-65

3. Boeve BF, Boylan KB, Graff-Radford NR, et al: Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 2012;135(Pt 3):765-783