C9orf72 and intracerebral hemorrhage

Isabel C Hostettler; Manuel Bernal-Quiros; Andrew Wong; Nikhil Sharma; Duncan Wilson; David J Seiffge; Clare Shakeshaft; Hans R Jäger; Hannah Cohen; Tarek Yousry; Rustam Al-Shahi Salman; Gregory Y H Lip; Martin M Brown; Keith W Muir; David J Werring; Henry Houlden; CROMIS-2 collaborators

doi:10.1016/j.neurobiolaging.2019.07.007

C9orf72 and intracerebral hemorrhage

Neurobiol Aging. 2019 Dec:84:237.e1-237.e3. doi: 10.1016/j.neurobiolaging.2019.07.007. Epub 2019 Jul 18.

Authors

Isabel C Hostettler¹, Manuel Bernal-Quiros², Andrew Wong³, Nikhil Sharma⁴, Duncan Wilson⁵, David J Seiffge⁶, Clare Shakeshaft⁵, Hans R Jäger⁷, Hannah Cohen⁸, Tarek Yousry⁷, Rustam Al-Shahi Salman⁹, Gregory Y H Lip¹⁰, Martin M Brown⁵, Keith W Muir¹¹, David J Werring⁵, Henry Houlden¹²; CROMIS-2 collaborators

Affiliations

¹ Stroke Research Centre, University College London, Institute of Neurology, London, UK; Neurogenetics Laboratory, The National Hospital of Neurology and Neurosurgery and UCL Institute of Neurology, London, UK.
² Neurogenetics Laboratory, The National Hospital of Neurology and Neurosurgery and UCL Institute of Neurology, London, UK.
³ MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
⁴ Department of Neurology, The National Hospital of Neurology and Neurosurgery, London, UK; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK.
⁵ Stroke Research Centre, University College London, Institute of Neurology, London, UK.
⁶ Stroke Research Centre, University College London, Institute of Neurology, London, UK; Stroke Centre and Institute of Neurology, University Hospital and University Basel, Basel, Switzerland; Department of Neurology and Stroke Center, Inselspital, University Hospital Bern, Bern, Switzerland.
⁷ Neuroradiological Academic Unit, Department of Brain Repair & Rehabilitation, University College London Institute of Neurology, London, UK.
⁸ Haemostasis Research Unit, Department of Haematology, University College London, London, UK.
⁹ Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
¹⁰ Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
¹¹ Institute of Neuroscience & Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
¹² Neurogenetics Laboratory, The National Hospital of Neurology and Neurosurgery and UCL Institute of Neurology, London, UK. Electronic address: h.houlden@ucl.ac.uk.

PMID: 31582231
DOI: 10.1016/j.neurobiolaging.2019.07.007

Abstract

The chromosome 9 open reading frame 72 (C9orf72) GGGGCC repeat expansion has been associated with several diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. It has also been associated with increased white matter changes in frontotemporal dementia and risk of cognitive impairment in ALS. Dementia is common both before and after intracerebral hemorrhage (ICH). Because the mechanisms of cognitive impairment in patients with ICH are uncertain, we investigated whether C9orf72 could influence dementia risk in this patient group. Therefore, we genotyped 1010 clinically characterized ICH cases and 2147 population controls in comparison with prior data of dementia and ALS cases. We did not find any association between C9orf72 repeat expansion and repeat size with ICH compared with controls or with dementia when assessing ICH patients only. The frequency of C9orf72 expansions in our series of individuals born in 1946 (2/2147) and other U.K. controls was age dependent, decreasing with increasing age, highlighting the high age-dependent penetrance of this expansion.

Keywords: C9orf72; Dementia; Genetics; Imaging markers; Intracerebral hemorrhage; White matter changes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C9orf72 Protein / genetics*
Cerebral Hemorrhage / genetics*
Humans

Substances

C9orf72 Protein
C9orf72 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding