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

Aleksandra Klimkowicz-Mrowiec, Anna Dziubek, Małgorzata Sado, Marek Karpiński and Agnieszka Gorzkowska
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Aleksandra Klimkowicz-Mrowiec: Department of Internal Medicine and Gerontology, Faculty of Medicine, Medical College, Jagiellonian University, 30-688 Krakow, Poland
Anna Dziubek: Haematological Diagnostics and Genetics Unit, University Hospital, 30-688 Krakow, Poland
Małgorzata Sado: Haematological Diagnostics and Genetics Unit, University Hospital, 30-688 Krakow, Poland
Marek Karpiński: Department of Internal Medicine and Gerontology, Faculty of Medicine, Medical College, Jagiellonian University, 30-688 Krakow, Poland
Agnieszka Gorzkowska: Department of Neurorehabilitation, Faculty of Medical Sciences, School of Medicine, Medical University of Silesia, 40-752 Katowice, Poland

IJERPH, 2021, vol. 18, issue 16, 1-7

Abstract: 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.

Keywords: Alzheimer’s disease; frontotemporal dementia; next generation sequencing; biomarkers; psychiatric disorder (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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