A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia

Roneil Malkani; Ian D'Souza; Katrina Gwinn-Hardy; Gerard D. Schellenberg; John Hardy; Parastoo Momeni

doi:10.1016/j.nbd.2005.12.001

A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia

Roneil Malkani, Ian D'Souza, Katrina Gwinn-Hardy, Gerard D. Schellenberg, John Hardy, Parastoo Momeni^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation co-segregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia.

Original language	English (US)
Pages (from-to)	401-403
Number of pages	3
Journal	Neurobiology of Disease
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2005.12.001
State	Published - May 2006

Funding

This work was supported by the NIA intramural program and by R01 AG1176 (GDS), NINDS Intramural (Gwinn-Hardy) as well as by an Alzheimer's Disease Research Grant from the American Health Assistance Foundation (ID). Thanks to Dr. Mike Hutton for his advice for this study.

Keywords

Frontotemporal dementia
MAPT
Splicing

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2005.12.001

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title = "A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia",

abstract = "We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation co-segregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia.",

keywords = "Frontotemporal dementia, MAPT, Splicing",

author = "Roneil Malkani and Ian D'Souza and Katrina Gwinn-Hardy and Schellenberg, {Gerard D.} and John Hardy and Parastoo Momeni",

note = "Funding Information: This work was supported by the NIA intramural program and by R01 AG1176 (GDS), NINDS Intramural (Gwinn-Hardy) as well as by an Alzheimer's Disease Research Grant from the American Health Assistance Foundation (ID). Thanks to Dr. Mike Hutton for his advice for this study.",

year = "2006",

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doi = "10.1016/j.nbd.2005.12.001",

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volume = "22",

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AU - D'Souza, Ian

AU - Gwinn-Hardy, Katrina

AU - Schellenberg, Gerard D.

AU - Hardy, John

AU - Momeni, Parastoo

N1 - Funding Information: This work was supported by the NIA intramural program and by R01 AG1176 (GDS), NINDS Intramural (Gwinn-Hardy) as well as by an Alzheimer's Disease Research Grant from the American Health Assistance Foundation (ID). Thanks to Dr. Mike Hutton for his advice for this study.

PY - 2006/5

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N2 - We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation co-segregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia.

AB - We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation co-segregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia.

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KW - Splicing

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A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia

Abstract

Funding

Keywords

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