A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene.
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ICR Authors
Authors
Olszewska, DA
Fearon, C
McGuigan, C
McVeigh, TP
Houlden, H
Polke, JM
Lawlor, B
Coen, R
Hutchinson, M
Hutton, M
Beausang, A
Delon, I
Brett, F
Sevastou, I
Seto-Salvia, N
de Silva, R
Lynch, T
Fearon, C
McGuigan, C
McVeigh, TP
Houlden, H
Polke, JM
Lawlor, B
Coen, R
Hutchinson, M
Hutton, M
Beausang, A
Delon, I
Brett, F
Sevastou, I
Seto-Salvia, N
de Silva, R
Lynch, T
Document Type
Journal Article
Date
2021-10-01
Date Accepted
2021-05-13
Abstract
We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease. This report of a second family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This intronic point mutation, probably strengthens the polypyrimidine tract and alters the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice site.
Citation
Neurobiology of Aging, 2021
Source Title
Publisher
ELSEVIER SCIENCE INC
ISSN
0197-4580