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. 2017 Jan:49:215.e1-215.e8.
doi: 10.1016/j.neurobiolaging.2016.09.008. Epub 2016 Sep 23.

Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array

Imelda S Barber  1 , Anne Braae  2 , Naomi Clement  2 , Tulsi Patel  2 , Tamar Guetta-Baranes  2 , Keeley Brookes  2 , Christopher Medway  2 , Sally Chappell  2 , Rita Guerreiro  3 , Jose Bras  3 , Dena Hernandez  4 , Andrew Singleton  4 , John Hardy  3 , David M Mann  5 ; ARUK Consortium; Kevin Morgan  2
Collaborators, Affiliations

Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array

Imelda S Barber et al. Neurobiol Aging. 2017 Jan.

Abstract

We have screened sporadic early-onset Alzheimer's disease (sEOAD, n = 408) samples using the NeuroX array for known causative and predicted pathogenic variants in 16 genes linked to familial forms of neurodegeneration. We found 2 sEOAD individuals harboring a known causative variant in PARK2 known to cause early-onset Parkinson's disease; p.T240M (n = 1) and p.Q34fs delAG (n = 1). In addition, we identified 3 sEOAD individuals harboring a predicted pathogenic variant in MAPT (p.A469T), which has previously been associated with AD. It is currently unknown if these variants affect susceptibility to sEOAD, further studies would be needed to establish this. This work highlights the need to screen sEOAD individuals for variants that are more classically attributed to other forms of neurodegeneration.

Keywords: Alzheimer's disease; Early-onset; NeuroX; Parkinson's disease; Screening; Sporadic.

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Conflict of interest statement

Disclosure statement

The authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Sequence chromatograms. Sequence chromatograms of all 13 individuals thought to harbor a pathogenic (A) or predicted pathogenic variant (B). Each individual was sequenced in forward (top row) and reverse (bottom row) orientations. Note that the forward orientation does not always correspond to the sense strand. The images were taken from Sequence Scanner (Applied Biosystems) with the variant at the centre and surrounded by 2 or 3 bases either side. Four individuals (M215, M697, M172, and M382) show wild-type sequence according to the chromatogram.
Fig. 2
Fig. 2
SNP cluster plot for genotypes unconfirmed with Sanger sequencing. SNP cluster graphs generated by Genome Studio for markers NeuroX_16:31196410 (p.G225V located in FUS) (A), exm1331018 (p.S427F located in MAPT) (B), and exm1331027 (p.A469T located in MAPT) (C). Each colored circle represents 1 individual, those colored red are homozygous mutant (TT), those colored purple are heterozygous (GT), those colored blue are homozygous wildtype (GG), and finally those colored black are not called. The plots show all 10 samples called as heterozygotes cluster well and do not explain why 4 samples failed to verify with Sanger sequencing (M215, M697, M172, and M382).
See this image and copyright information in PMC

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