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

Ashley Crook*, Alison McEwen, Jennifer A. Fifita, Katharine Zhang, John B. Kwok, Glenda Halliday, Ian P. Blair, Dominic B. Rowe

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)310-316
Number of pages7
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number5-6
Early online date23 Mar 2019
Publication statusPublished - Jul 2019


  • C9orf72
  • genetic counseling
  • Genetic testing
  • genetics
  • intermediate expansions
  • laboratory methods
  • repeat expansions


Dive into the research topics of 'The C9orf72 hexanucleotide repeat expansion presents a challenge for testing laboratories and genetic counseling'. Together they form a unique fingerprint.

Cite this