Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

A recent study by Bannwarth et al. implicated CHCHD10 as a novel gene for Amyotrophic Lateral Sclerosis/Frontotemporal
Lobar Degeneration (ALS/FTLD). Affected family members were presented with a complex phenotype that included
symptoms of ALS, FTLD, cerebellar ataxia, Parkinson’s Disease (PD) and a mitochondrial myopathy associated with multiple
mitochondrial DNA deletions. So far, seven mis-sense CHCHD10 mutations have been reported in patients with a broad
phenotypic range. Notably, mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Hence, we
sequenced CHCHD10 in 204 ALS, 153 PD, 158 FTLD and 141 Alzheimer’s Disease (AD) patients as well as 497 normal controls.
We identified two known pathogenic mutations in three ALS patients (p.R15L and p.P80L) as well as two novel substitutions
in two FTLD patients (p.P23T and p.A35D). Finally, we detected a p.P34S substitution in PD patient who has no symptoms of
muscle weakness, dementia or ALS. The same p.P34S variant was also detected in two AD cases but it did not segregate with
AD in the available family. The p.P34S variant was previously reported in unrelated FTLD/ALS and ALS patients. However,
the p.P34S substitution was found at comparable frequencies in our control samples and public databases suggesting that this
variant is not pathogenic which is important in the utility of genetic screening in patient care. The frequency of the CHCHD10
mutations in our datasets is 2.6% for familial ALS, 1.2% for sporadic ALS, 1.6% for familial FTLD and 1% for sporadic FTLD.
All mutation carriers are characterized by atypically long duration and slow disease progression. In conclusion, our study
supports the causal role of CHCHD10 mutations in both ALS and FTLD but not in AD or PD. Intriguingly, the mutations
in the CHCHD2 gene (structurally similar to CHCHD10) were very recently reported to cause PD in Japanese patients. The
mutation analysis of CHCHD2 in Canadian PD dataset is ongoing and will be presented.

Biography

Ekaterina Rogaeva obtained her PhD in Biochemistry at Moscow State University (Russia) in 1988. Since 1992, she has been conducting molecular genetics
research on neurodegenerative diseases at the University of Toronto and the Tanz CRND. In 2002, she became an Assistant Professor and currently (since 2008),
she is an Associate Professor in the Department of Medicine at the University of Toronto. In 2013, she also obtained a Chair Position in Research on Dementia with
Lewy Bodies at Tanz CRND. In 2001, she was the recipient the ‘New Pioneer Award’ in Science & Technology category (Government of Ontario).