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

Diana A. Olszewska; Conor Fearon; Christopher McGuigan; Terri P. McVeigh; Henry Houlden; James M. Polke; Brian Lawlor; Robert Coen; Michael Hutchinson; Michael Hutton; Alan Beausang; Isabelle Delon; Francesca Brett; Ioanna Sevastou; Nuria Seto-Salvia; Rohan de Silva; Tim Lynch

doi:10.1016/j.neurobiolaging.2021.05.010

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

Diana A. Olszewska, Conor Fearon, Christopher McGuigan, Terri P. McVeigh, Henry Houlden, James M. Polke, Brian Lawlor, Robert Coen, Michael Hutchinson, Michael Hutton, Alan Beausang, Isabelle Delon, Francesca Brett, Ioanna Sevastou, Nuria Seto-Salvia, Rohan de Silva, Tim Lynch

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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.

Original language	English
Pages (from-to)	343.e1-343.e8
Journal	Neurobiology of Aging
Volume	106
DOIs	https://doi.org/10.1016/j.neurobiolaging.2021.05.010
State	Published - Oct 2021
Externally published	Yes

Keywords

Frontotemporal dementia
Genetics
Intron 9/exon 10 mutation
Neuropathology
c.823-10G>T

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10.1016/j.neurobiolaging.2021.05.010

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Olszewska, D. A., Fearon, C., McGuigan, C., McVeigh, T. P., Houlden, H., Polke, J. M., Lawlor, B., Coen, R., Hutchinson, M., Hutton, M., Beausang, A., Delon, I., Brett, F., Sevastou, I., Seto-Salvia, N., de Silva, R., & Lynch, T. (2021). 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. Neurobiology of Aging, 106, 343.e1-343.e8. https://doi.org/10.1016/j.neurobiolaging.2021.05.010

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title = "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",

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{\textquoteright} splice site.",

keywords = "Frontotemporal dementia, Genetics, Intron 9/exon 10 mutation, Neuropathology, c.823-10G>T",

author = "Olszewska, {Diana A.} and Conor Fearon and Christopher McGuigan and McVeigh, {Terri P.} and Henry Houlden and Polke, {James M.} and Brian Lawlor and Robert Coen and Michael Hutchinson and Michael Hutton and Alan Beausang and Isabelle Delon and Francesca Brett and Ioanna Sevastou and Nuria Seto-Salvia and {de Silva}, Rohan and Tim Lynch",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = oct,

doi = "10.1016/j.neurobiolaging.2021.05.010",

language = "English",

volume = "106",

pages = "343.e1--343.e8",

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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 2021, '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', Neurobiology of Aging, vol. 106, pp. 343.e1-343.e8. https://doi.org/10.1016/j.neurobiolaging.2021.05.010

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AU - Olszewska, Diana A.

AU - Fearon, Conor

AU - McGuigan, Christopher

AU - McVeigh, Terri P.

AU - Houlden, Henry

AU - Polke, James M.

AU - Lawlor, Brian

AU - Coen, Robert

AU - Hutchinson, Michael

AU - Hutton, Michael

AU - Beausang, Alan

AU - Delon, Isabelle

AU - Brett, Francesca

AU - Sevastou, Ioanna

AU - Seto-Salvia, Nuria

AU - de Silva, Rohan

AU - Lynch, Tim

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

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KW - Genetics

KW - Intron 9/exon 10 mutation

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AN - SCOPUS:85110435277

SN - 0197-4580

VL - 106

SP - 343.e1-343.e8

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

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

Abstract

Keywords

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