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Compound heterozygosity of 2 novel MAPT mutations in frontotemporal dementia

Anfossi, M., Vuono, Romina, Maletta, R., Virdee, K., Mirabelli, M., Colao, R., Puccio, G., Bernardi, L., Frangipane, F., Gallo, M., and others. (2011) Compound heterozygosity of 2 novel MAPT mutations in frontotemporal dementia. Neurobiology of Aging, 32 (4). 757.e1-757.e11. ISSN 0197-4580. (doi:10.1016/j.neurobiolaging.2010.12.013) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:79841)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
https://doi.org/10.1016/j.neurobiolaging.2010.12.0...

Abstract

Intronic MAPT mutations altering exon 10 splicing lead mainly to an increase of 4Rtau. The objective of this study is to report clinical, genetic, and neuropathological data of an apparently sporadic early onset frontotemporal dementia (FTD) case associated with 2 novel intronic MAPT gene mutations IVS10+4A > C and IVS9-15T > C that increase 3Rtau. Methods and subjects used are clinical, neuroradiological, and neuropathological examination; molecular genetics of MAPT, PGRN, and other relevant genes. Exon 10 splicing tested with minigene constructs. Tau deposits detected by immunohistochemistry. Sarkosyl-insoluble and soluble tau investigated by immunoblotting. Two novel MAPT mutations IVS10+4A > C and the IVS9-15T > C transmitted by the unaffected parents were identified. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analyses on minigenes and in brain tissue showed that both mutations cause an increase of tau mRNA (messenger ribonucleic acid) transcripts lacking exon 10 only in the patient. Immunohistochemistry and immunoblotting of the patient's brain revealed tau deposits composed mostly of 3Rtau isoforms with a predominance of the shorter 3Rtau isoforms. The compound heterozygosity of the patient increasing 3Rtau seems to be responsible for the disease and furthermore suggests that sporadic cases can be caused by genetic mutations.

Item Type: Article
DOI/Identification number: 10.1016/j.neurobiolaging.2010.12.013
Uncontrolled keywords: adenine; cytosine; isoprotein; messenger RNA; tau protein; thymine, adult; article; case report; disease transmission; exon; female; frontotemporal dementia; gene; gene construct; gene mutation; homozygosity; human; human tissue; intron; mapt gene; molecular genetics; onset age; PGRN gene; priority journal; protein localization; RNA splicing
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Romina Vuono
Date Deposited: 29 Jan 2020 10:58 UTC
Last Modified: 20 Feb 2020 09:56 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/79841 (The current URI for this page, for reference purposes)
Vuono, Romina: https://orcid.org/0000-0002-5162-3422
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