Spinocerebellar Ataxia-Like Presentation of the M233V PSEN1 Mutation
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SHORT REPORTS
Spinocerebellar Ataxia-Like Presentation of the M233V PSEN1 Mutation Yury Seliverstov 1
&
Ilya Kanivets 2 & Sergey Illarioshkin 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract PSEN1 gene is considered to be the most common gene, which is responsible for the development of an autosomal dominant Alzheimer disease with early onset and sometimes broad phenotype. We present a patient with a spinocerebellar ataxia (SCA)-like phenotype who was found to carry an M233V mutation. General and neurological exam was carried out. Brain MRI as well as genetic testing for SCAs 1, 2, 3, 6, and 17 were performed. The patient was then referred for a next-generation sequencing-based gene panel test with 723 genes included. A 26-year-old man of an Azerbaijani origin presented with a progressive impairment of coordination followed by memory impairment. Family history was positive for a similar disorder suggesting autosomal dominant inheritance. Brain MRI showed bilateral hippocampal atrophy (more pronounced in the left), as well as mild atrophy of the left temporoparietal cortex. Tests for SCAs 1, 2, 3, 6, and 17 came negative. Gene panel test showed c.697A > G heterozygous variant in the PSEN1 gene leading to a M233V amino acid change, which was validated by a Sanger sequencing. So far, M233V mutation has not been associated with a combination of cerebellar and cognitive features at onset. Our case contributes to a better characterization of the PSEN1 mutations and expands the phenotype of the M233V carriers. We propose to consider PSEN1 mutations in patients presenting with an SCA-like phenotype but negative for common types of SCA. Keywords Ataxia . Alzheimer disease . Mutation . Genetic testing
Introduction PSEN1 gene is located on the long arm of chromosome 14 and encodes a presenilin-1 protein, which is a part of the gammasecretase tetrameric complex. The latter is crucial for cleaving a large number of transmembrane proteins, including amyloid precursor protein (APP) and Notch receptors [1]. In humans, mutations in the PSEN1 gene are associated with a familial early-onset Alzheimer disease (AD). It is considered to be the most common gene, which is responsible for the development of a familial autosomal dominant AD with onset usually
between 30 and 50 years (in rare cases, even earlier) and almost complete penetrance [2]. So far, over 300 pathogenic PSEN1 mutations have been described, according to the Alzforum database (https://www.alzforum.org). We present a patient with a spinocerebellar ataxia (SCA)-like phenotype, who was found to carry a pathogenic mutation in the PSEN1 gene.
Methods Case
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12311-020-01161-3) contains supplementary material, which is available to authorized users. * Yury Seliverstov [email protected] 1
Research Center of Neurology, Moscow, Russia
2
Genomed Ltd., Moscow, Russia
A 26-year-old man of an Azerbaijani origin presented to the Research Center o
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