Session Information
Date: Tuesday, June 21, 2016
Session Title: Genetics (NON-PD)
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To investigate MAPT variants and haplotypes, GRN mutations, and C9orf72 expansion in a cohort of Russian patients with progressive supranuclear palsy (PSP), cotricobasal syndrome (CBS) and frontotemporal lobar degeneration (FTLD).
Background: PSP, CBS and FTLD have much in common in clinical (progressive cognitive decline and parkinsonism) and morphological (tauopathy spectrum) presentations, and they are characterized by overlapping genetic basis. PSP is associated with the MAPT H1-haplotype and mutations in this gene. FTLD is caused by mutations in GRN gene and by expansion in recently discovered C9orf72 gene. According to some studies, all three genes may be implicated in CBS.
Methods: We studied 34 Russian patients with PSP (n=13), CBS (n=8) and FTLD (n=13, behavioral variant of frontotemporal dementia and primary progressive aphasia). All exons of MAPT and GRN genes and MAPT haplotype-specific polymorphisms were analyzed using direct sequencing. Expansions of hexanucleotide repeats in C9orf72 were assessed by repeat-primed PCR.
Results: We identified 58 different polymorphisms across MAPT, including 5 novel variants and 19 known variants in exons 4a, 6-10 (12 variants causing amino acid replacement and 5 were defined as ‘damaging’ by SIFT and/or PolyPhen2). MAPT variants occurred in patients with different syndromes (PSP/CBS/FTLD). H1/H1-haplotype was found in 27 PSP/CBS/FTLD patients and H1/H2-haplotype in 5 PSP/CBS/FTLD patients. On analysis of GRN gene, we found 2 intron variants (rs398030920 in 15 PSP/CBS/FTLD cases and rs9897526 in one PSP case) and 2 exon variants (rs25646 in one FTLD case and rs748764855 in one FTLD case). The latter variant was defined as ‘damaging’ with SIFT and was identified in one sporadic FTLD case. There were no C9orf72 expansions in PSP/CBS/FTLD, possibly due to a small number of FTLD cases in our cohort.
Conclusions: Overlapping phenotypical spectrum and complex genetic basis of PSP/CBS/FTLD justify screening of all relevant genes in every patient. This work was supported by the Ministry of Science and Education of Russia; UID number RFMEFI60714X0094.
To cite this abstract in AMA style:
E.Y. Fedotova, N.Y. Abramycheva, M.S. Stepanova, A.S. Vetchinova, S.N. Illarioshkin. Analysis of MAPT, GRN and C9orf72 genes in progressive supranuclear palsy, corticobasal syndrome and frontotemporal lobar degeneration in Russian population [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/analysis-of-mapt-grn-and-c9orf72-genes-in-progressive-supranuclear-palsy-corticobasal-syndrome-and-frontotemporal-lobar-degeneration-in-russian-population/. Accessed June 14, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-mapt-grn-and-c9orf72-genes-in-progressive-supranuclear-palsy-corticobasal-syndrome-and-frontotemporal-lobar-degeneration-in-russian-population/