PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea

PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea

Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medi...

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Autores principales: Bagyinszky E, Park SA, Kim HJ, Choi SH, An SSA, Kim SY
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2016
Materias:
Alzheimer’s disease
PSEN1 mutation
sequencing
frontotemporal dementia
Geriatrics
RC952-954.6
Acceso en línea:https://doaj.org/article/34706bb5ee654c7399841ad8188ae70c
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spelling oai:doaj.org-article:34706bb5ee654c7399841ad8188ae70c2021-12-02T06:13:22ZPSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea1178-1998https://doaj.org/article/34706bb5ee654c7399841ad8188ae70c2016-10-01T00:00:00Zhttps://www.dovepress.com/psen1-l226f-mutation-in-a-patient-with-early-onset-alzheimerrsquos-dis-peer-reviewed-article-CIAhttps://doaj.org/toc/1178-1998Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medicine, Incheon, 4Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we report a first 226leucine (Leu) mutation to phenylalanine (Phe) in (PSEN1, CTC>TTC, L226F) in Asia from a Korean early-onset Alzheimer’s disease (EOAD) patient. Polymerase chain reaction (PCR)–single strand conformation polymorphism, sequencing, and in silico predictions were performed. Previously, L226F was reported in EOAD patients by Zekanowski et al and Gómez-Tortosa et al. Disease phenotypes appeared in their thirties, and family history was positive in both cases. In our patient, age of onset was similar (37 years of age), but the mutation seemed to be de novo, since no affected family member was found. This leucine to phenylalanine substitution may cause additional stresses inside the transmembrane region due to large aromatic side chain and increased hydrophobic interactions with hydrocarbon chains in the membrane and its binding partners. Clinical phenotype of the mutation was aggressive progression into neurodegeneration, resulting in rapid cognitive decline. One of the patients was initially diagnosed with frontotemporal dementia, but the diagnosis was revised to AD upon postmortem studies in which Aβ plaques were seen. A second mutation, L226R, was found for the L226 residue. Similar to L226F, the patient with L226R also developed the first symptoms in his 30s, but EOAD was diagnosed in his 40s. These findings suggested that L226 might be an important residue in PSEN1, since mutations could result in neurodegenerative disease phenotypes at relatively young ages. There are mutations, such as L226F, which may not present clear clinical symptoms for the definitive diagnosis between frontotemporal dementia and AD. In addition, the similarities in the phenotypes could also be possible between AD and frontotemporal dementia, suggesting difficulties in differential diagnosis of various neurodegenerative diseases. Keywords: Alzheimer’s disease, PSEN1 mutation, sequencing, frontotemporal dementiaBagyinszky EPark SAKim HJChoi SHAn SSAKim SYDove Medical PressarticleAlzheimer’s diseasePSEN1 mutationsequencingfrontotemporal dementiaGeriatricsRC952-954.6ENClinical Interventions in Aging, Vol Volume 11, Pp 1433-1440 (2016)
institution DOAJ
collection DOAJ
language EN
topic Alzheimer’s disease
PSEN1 mutation
sequencing
frontotemporal dementia
Geriatrics
RC952-954.6
spellingShingle Alzheimer’s disease
PSEN1 mutation
sequencing
frontotemporal dementia
Geriatrics
RC952-954.6
Bagyinszky E
Park SA
Kim HJ
Choi SH
An SSA
Kim SY
PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
description Eva Bagyinszky,1,* Sun Ah Park,2,* Hyung Jun Kim,2 Seong Hye Choi,3 Seong Soo A An,1 SangYun Kim4 1Department of BioNano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Inha University School of Medicine, Incheon, 4Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: In this study, we report a first 226leucine (Leu) mutation to phenylalanine (Phe) in (PSEN1, CTC>TTC, L226F) in Asia from a Korean early-onset Alzheimer’s disease (EOAD) patient. Polymerase chain reaction (PCR)–single strand conformation polymorphism, sequencing, and in silico predictions were performed. Previously, L226F was reported in EOAD patients by Zekanowski et al and Gómez-Tortosa et al. Disease phenotypes appeared in their thirties, and family history was positive in both cases. In our patient, age of onset was similar (37 years of age), but the mutation seemed to be de novo, since no affected family member was found. This leucine to phenylalanine substitution may cause additional stresses inside the transmembrane region due to large aromatic side chain and increased hydrophobic interactions with hydrocarbon chains in the membrane and its binding partners. Clinical phenotype of the mutation was aggressive progression into neurodegeneration, resulting in rapid cognitive decline. One of the patients was initially diagnosed with frontotemporal dementia, but the diagnosis was revised to AD upon postmortem studies in which Aβ plaques were seen. A second mutation, L226R, was found for the L226 residue. Similar to L226F, the patient with L226R also developed the first symptoms in his 30s, but EOAD was diagnosed in his 40s. These findings suggested that L226 might be an important residue in PSEN1, since mutations could result in neurodegenerative disease phenotypes at relatively young ages. There are mutations, such as L226F, which may not present clear clinical symptoms for the definitive diagnosis between frontotemporal dementia and AD. In addition, the similarities in the phenotypes could also be possible between AD and frontotemporal dementia, suggesting difficulties in differential diagnosis of various neurodegenerative diseases. Keywords: Alzheimer’s disease, PSEN1 mutation, sequencing, frontotemporal dementia
format article
author Bagyinszky E
Park SA
Kim HJ
Choi SH
An SSA
Kim SY
author_facet Bagyinszky E
Park SA
Kim HJ
Choi SH
An SSA
Kim SY
author_sort Bagyinszky E
title PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
title_short PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
title_full PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
title_fullStr PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
title_full_unstemmed PSEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea
title_sort psen1 l226f mutation in a patient with early-onset alzheimer’s disease in korea
publisher Dove Medical Press
publishDate 2016
url https://doaj.org/article/34706bb5ee654c7399841ad8188ae70c
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