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The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia

The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis...

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Autores principales: Klimkowicz-Mrowiec, Aleksandra, Dziubek, Anna, Sado, Małgorzata, Karpiński, Marek, Gorzkowska, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392561/
https://www.ncbi.nlm.nih.gov/pubmed/34444269
http://dx.doi.org/10.3390/ijerph18168520
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author Klimkowicz-Mrowiec, Aleksandra
Dziubek, Anna
Sado, Małgorzata
Karpiński, Marek
Gorzkowska, Agnieszka
author_facet Klimkowicz-Mrowiec, Aleksandra
Dziubek, Anna
Sado, Małgorzata
Karpiński, Marek
Gorzkowska, Agnieszka
author_sort Klimkowicz-Mrowiec, Aleksandra
collection PubMed
description The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis than is assumed. Two patients, at different times, presented to the Memory Clinic because of memory problems and difficulty in performing daily activities and work. Neither caregiver complained of marked behavioural or personality changes, except for apathy. Patients underwent standard dementia evaluation procedures including clinical symptoms, family history, neuroimaging, neuropsychological evaluation, and genetic analysis of selected genes. Based on specific clinical phenotypes and genetic analysis of selected genes, both patients were diagnosed with frontal variant of Alzheimer’s disease. The presence of a rare polymorphism in PSEN2 in both patients allowed the discovery that they belong to the same family. This fact reinforced the belief that there is a strong genetic factor responsible for causing dementia in the family. Next-generation sequencing based on a panel of 118 genes was performed to identify other potential genetic factors that may determine the background of the disease. A mutation in the GRN gene was identified, and the previous diagnosis was changed to frontotemporal dementia. The described cases show how important it is to combine all diagnostic tests available in the diagnostic centre, including new generation genetic tests, in order to establish/confirm the pathological background of clinical symptoms of dementia. If there is any doubt about the final diagnosis, persistent efforts should be made to verify the cause.
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spelling pubmed-83925612021-08-28 The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia Klimkowicz-Mrowiec, Aleksandra Dziubek, Anna Sado, Małgorzata Karpiński, Marek Gorzkowska, Agnieszka Int J Environ Res Public Health Case Report The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis than is assumed. Two patients, at different times, presented to the Memory Clinic because of memory problems and difficulty in performing daily activities and work. Neither caregiver complained of marked behavioural or personality changes, except for apathy. Patients underwent standard dementia evaluation procedures including clinical symptoms, family history, neuroimaging, neuropsychological evaluation, and genetic analysis of selected genes. Based on specific clinical phenotypes and genetic analysis of selected genes, both patients were diagnosed with frontal variant of Alzheimer’s disease. The presence of a rare polymorphism in PSEN2 in both patients allowed the discovery that they belong to the same family. This fact reinforced the belief that there is a strong genetic factor responsible for causing dementia in the family. Next-generation sequencing based on a panel of 118 genes was performed to identify other potential genetic factors that may determine the background of the disease. A mutation in the GRN gene was identified, and the previous diagnosis was changed to frontotemporal dementia. The described cases show how important it is to combine all diagnostic tests available in the diagnostic centre, including new generation genetic tests, in order to establish/confirm the pathological background of clinical symptoms of dementia. If there is any doubt about the final diagnosis, persistent efforts should be made to verify the cause. MDPI 2021-08-12 /pmc/articles/PMC8392561/ /pubmed/34444269 http://dx.doi.org/10.3390/ijerph18168520 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Klimkowicz-Mrowiec, Aleksandra
Dziubek, Anna
Sado, Małgorzata
Karpiński, Marek
Gorzkowska, Agnieszka
The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title_full The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title_fullStr The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title_full_unstemmed The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title_short The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia
title_sort utility of next-generation sequencing for identifying the genetic basis of dementia
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392561/
https://www.ncbi.nlm.nih.gov/pubmed/34444269
http://dx.doi.org/10.3390/ijerph18168520
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