Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review
Background: Microtubule-associated protein tau (MAPT) mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2024-01-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901012 |
| _version_ | 1797338850857582592 |
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| author | Cristina Villa Elisa Pellencin Aurora Romeo Giorgio Giaccone Giacomina Rossi Sara Prioni Paola Caroppo |
| author_facet | Cristina Villa Elisa Pellencin Aurora Romeo Giorgio Giaccone Giacomina Rossi Sara Prioni Paola Caroppo |
| author_sort | Cristina Villa |
| collection | DOAJ |
| description | Background: Microtubule-associated protein tau (MAPT) mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported as single cases. In this review, we provide an overview of the clinical phenotypes associated with MAPT mutations in order to define their characteristics and explore genotype-phenotype correlations. Methods: We performed systematic bibliographic research on the Pubmed database, focusing on articles published between 1998 and 2022. We analysed the clinical phenotype of 177 patients carrying MAPT mutations, focusing on the rarest ones. We performed a narrative synthesis of the results. Results: Regarding language phenotypes, the most frequent were the non-fluent variant and the semantic variant of Primary Progressive Aphasia (nfvPPA, svPPA), approximately in the same proportion. Almost 20% of the whole group of patients present a clinical phenotype belonging to the corticobasal syndrome-progressive supranuclear palsy (CBS-PSP) spectrum. While no clear genotype-phenotype correlation could be identified, some mutations were associated with a specific phenotype, while others gave origin to multiple clinical pictures and mixed phenotypes. Conclusions: A high clinical heterogeneity exists in FTD associated with MAPT mutations without a clear phenotype-genotype correlation in most cases. However, some characteristics can be helpful to drive genetic testing. Deep phenotyping of patients, together with functional studies of single mutations, particularly those associated with atypical phenotypes, are necessary to better understand the biological mechanisms underlying this clinical variability. |
| first_indexed | 2024-03-08T09:37:20Z |
| format | Article |
| id | doaj.art-f2599b4db4364dbfb307d48552e799e8 |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-08T09:37:20Z |
| publishDate | 2024-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-f2599b4db4364dbfb307d48552e799e82024-01-30T07:44:34ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-01-012911210.31083/j.fbl2901012S2768-6701(23)01092-4Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic ReviewCristina Villa0Elisa Pellencin1Aurora Romeo2Giorgio Giaccone3Giacomina Rossi4Sara Prioni5Paola Caroppo6Neurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyNeurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyNeurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyNeurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyNeurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyClinical Neuropsychology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyNeurology V and Neuropathology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, ItalyBackground: Microtubule-associated protein tau (MAPT) mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported as single cases. In this review, we provide an overview of the clinical phenotypes associated with MAPT mutations in order to define their characteristics and explore genotype-phenotype correlations. Methods: We performed systematic bibliographic research on the Pubmed database, focusing on articles published between 1998 and 2022. We analysed the clinical phenotype of 177 patients carrying MAPT mutations, focusing on the rarest ones. We performed a narrative synthesis of the results. Results: Regarding language phenotypes, the most frequent were the non-fluent variant and the semantic variant of Primary Progressive Aphasia (nfvPPA, svPPA), approximately in the same proportion. Almost 20% of the whole group of patients present a clinical phenotype belonging to the corticobasal syndrome-progressive supranuclear palsy (CBS-PSP) spectrum. While no clear genotype-phenotype correlation could be identified, some mutations were associated with a specific phenotype, while others gave origin to multiple clinical pictures and mixed phenotypes. Conclusions: A high clinical heterogeneity exists in FTD associated with MAPT mutations without a clear phenotype-genotype correlation in most cases. However, some characteristics can be helpful to drive genetic testing. Deep phenotyping of patients, together with functional studies of single mutations, particularly those associated with atypical phenotypes, are necessary to better understand the biological mechanisms underlying this clinical variability.https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901012maptftdprimary progressive aphasiaadcbspspphenotypes |
| spellingShingle | Cristina Villa Elisa Pellencin Aurora Romeo Giorgio Giaccone Giacomina Rossi Sara Prioni Paola Caroppo Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review Frontiers in Bioscience-Landmark mapt ftd primary progressive aphasia ad cbs psp phenotypes |
| title | Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review |
| title_full | Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review |
| title_fullStr | Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review |
| title_full_unstemmed | Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review |
| title_short | Dissecting the Clinical Heterogeneity and Genotype-Phenotype Correlations of MAPT Mutations: A Systematic Review |
| title_sort | dissecting the clinical heterogeneity and genotype phenotype correlations of mapt mutations a systematic review |
| topic | mapt ftd primary progressive aphasia ad cbs psp phenotypes |
| url | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901012 |
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