C9ORF72 expansion in a family with bipolar disorder
Article first published online: 1 APR 2013
© 2013 John Wiley and Sons A/S. Published by Blackwell Publishing Ltd
Volume 15, Issue 3, pages 326–332, May 2013
How to Cite
C9ORF72 expansion in a family with bipolar disorder. Bipolar Disord 2013: 15: 326–332. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd., , , , , , , , , , .
- Issue published online: 3 MAY 2013
- Article first published online: 1 APR 2013
- Manuscript Accepted: 13 JAN 2013
- Manuscript Received: 9 OCT 2012
- atypical bipolar;
- repeat expansion
To investigate the role in bipolar disorder of the C9ORF72 hexanucleotide repeat expansion responsible for frontotemporal lobe dementia and amyotrophic lateral sclerosis.
Eighty-nine subjects from a previously described panel of individuals with bipolar disorder ascertained for genetic studies were screened to detect expansion of the C9ORF72 repeat. One two-generation family with bipolar disorder and an expanded repeat was characterized in depth using molecular diagnostics, imaging, histopathology, and neurological and neuropsychological evaluation.
One proband, with the typical clinical presentation of bipolar disorder, carried an expanded C9ORF72 allele of heterogeneous length between 14 and 20 kilobases (kb) as assessed by Southern blot. The expanded allele was inherited from a parent with atypical, late onset clinical features of bipolar disorder, who subsequently progressed to frontotemporal lobe dementia. The expansion in peripheral blood of the parent ranged from 8.5 to 20 kb. Cultured lymphoblastoid cells from this parent exhibited a homogeneous expansion of only 8.5 kb.
The disease course in the two generations described here demonstrates that expansion of the C9ORF72 may be associated with a form of bipolar disorder that presents clinically with classic phenomenology and progression to neurodegenerative disease. The frequency in our bipolar disorder cohort was only 1%, indicating that C9ORF72 is not a major contributor to bipolar disorder. DNA from cultured cells may be biased towards shorter repeats and nonrepresentative of the endogenous C9ORF72 expansion.