Spinocerebellar Ataxia-Like Presentation of the M233V PSEN1 Mutation

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.