ИСТИНА

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.