Researchers have recently found a single gene cause for two neurodegenerative conditions that are distinct but related, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In an online issue of the scientific journal Neuron, researchers at Mayo Clinic in Florida, in collaboration with the UCSF Memory and Aging Center and others, report that the newly discovered genetic abnormality is responsible for a significant proportion of families with both FTD and ALS (FTD/ALS) and many families where the dominant syndrome is either familial FTD or familial ALS. Less commonly, it is associated with sporadic FTD or sporadic ALS, meaning occurrences of FTD or ALS without a family history.

gene C9ORF72 on chromosome 9

An expanded repeat in gene C9ORF72 on chromosome 9 has been linked to frontotemporal dementia and amyotrophic lateral sclerosis.

Identification of the genetic abnormality marks the culmination of many years of investigation, a discovery that has been highly anticipated since researchers began in 2006 to publish evidence that a region on chromosome 9 was responsible for the pattern of disease in families with FTD and ALS. Our collaborative group has now narrowed down the region on chromosome 9 to a single gene called C9ORF72. The abnormality or mutation within the C9ORF72 gene is called an expanded repeat, which describes a short DNA sequence that is abnormally repeated hundreds to thousands of times, one sequence right after another, resulting in a long abnormal stretch of DNA that is not observed in individuals without disease. How this expanded repeat mutation leads to FTD, ALS, or both, however, remains a mystery. The function of the gene on chromosome 9 is not known, and its exact role in disease has yet to be identified.

The C9ORF72 gene is one of the few that have been implicated in the co-occurrence of FTD and ALS, but the expanded repeat mutation does not explain all cases of FTD/ALS, familial FTD, or familial ALS. In addition, the vast majority of sporadic FTD or sporadic ALS occurs for reasons we still do not completely understand.

The finding offers great potential to improve our understanding of FTD/ALS. We are hopeful that it will lead to future advances in disease-specific management or even treatment, and we are indebted to our research participants whose generosity of time and support have been invaluable to this recent discovery.

We are pleased to share with you this promising breakthrough in neurodegenerative disease research and are optimistic about the discovery’s potential clinical significance. Presently, genetic testing for the C9ORF72 abnormality is not yet clinically available, because laboratories that intend to provide testing must further refine the test and obtain FDA approval (called CLIA-certification) before it can be offered to the public. Please feel free to contact us by email for more information: genetics@memory.ucsf.edu.

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