The C9orf72 hexanucleotide repeat expansion presents a challenge for testing laboratories and genetic counseling

C9orf72 hexanucleotide repeat expansions are the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Genetic testing for C9orf72 expansions in patients with ALS and/or FTD and their relatives has become increasingly available since hexanucleotide repeat...

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Bibliographic Details
Published in:Amyotrophic lateral sclerosis and frontotemporal degeneration 2019-07, Vol.20 (5-6), p.310-316
Main Authors: Crook, Ashley, McEwen, Alison, Fifita, Jennifer A., Zhang, Katharine, Kwok, John B., Halliday, Glenda, Blair, Ian P., Rowe, Dominic B.
Format: Article
Language:English
Subjects:
Adult
Amyotrophic Lateral Sclerosis - diagnosis
Amyotrophic Lateral Sclerosis - genetics
C9orf72
C9orf72 Protein - genetics
DNA Repeat Expansion - genetics
Female
genetic counseling
Genetic Counseling - methods
Genetic Counseling - standards
Genetic testing
Genetic Testing - methods
Genetic Testing - standards
genetics
Humans
intermediate expansions
laboratory methods
Pedigree
repeat expansions
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Summary:C9orf72 hexanucleotide repeat expansions are the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Genetic testing for C9orf72 expansions in patients with ALS and/or FTD and their relatives has become increasingly available since hexanucleotide repeat expansions were first reported in 2011. The repeat number is highly variable and the threshold at which repeat size leads to neurodegeneration remains unknown. We present the case of an ALS patient who underwent genetic testing through our Motor Neurone Disease Clinic. We highlight current limitations to analysing and interpreting C9orf72 expansion test results and describe how this resulted in discordant reports of pathogenicity between testing laboratories that confounded the genetic counselling process. We conclude that patients with ALS or FTD and their at-risk family members, need to be adequately counselled about the limitations of current knowledge to ensure they are making informed decisions about genetic testing for C9orf72. Greater collaboration between clinicians, testing laboratories and researchers is required to ensure risks to patients and their families are minimised.
ISSN:2167-8421
2167-9223
DOI:10.1080/21678421.2019.1588904