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Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders

We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD...

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Autores principales: Napolioni, Valerio, Fredericks, Carolyn A., Kim, Yongha, Channappa, Divya, Khan, Raiyan R., Kim, Lily H., Zafar, Faria, Couthouis, Julien, Davidzon, Guido A., Mormino, Elizabeth C., Gitler, Aaron D., Montine, Thomas J., Schüle, Birgitt, Greicius, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774039/
https://www.ncbi.nlm.nih.gov/pubmed/35052839
http://dx.doi.org/10.3390/biomedicines10010160
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author Napolioni, Valerio
Fredericks, Carolyn A.
Kim, Yongha
Channappa, Divya
Khan, Raiyan R.
Kim, Lily H.
Zafar, Faria
Couthouis, Julien
Davidzon, Guido A.
Mormino, Elizabeth C.
Gitler, Aaron D.
Montine, Thomas J.
Schüle, Birgitt
Greicius, Michael D.
author_facet Napolioni, Valerio
Fredericks, Carolyn A.
Kim, Yongha
Channappa, Divya
Khan, Raiyan R.
Kim, Lily H.
Zafar, Faria
Couthouis, Julien
Davidzon, Guido A.
Mormino, Elizabeth C.
Gitler, Aaron D.
Montine, Thomas J.
Schüle, Birgitt
Greicius, Michael D.
author_sort Napolioni, Valerio
collection PubMed
description We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson’s disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher’s disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features.
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spelling pubmed-87740392022-01-21 Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders Napolioni, Valerio Fredericks, Carolyn A. Kim, Yongha Channappa, Divya Khan, Raiyan R. Kim, Lily H. Zafar, Faria Couthouis, Julien Davidzon, Guido A. Mormino, Elizabeth C. Gitler, Aaron D. Montine, Thomas J. Schüle, Birgitt Greicius, Michael D. Biomedicines Article We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson’s disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher’s disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features. MDPI 2022-01-12 /pmc/articles/PMC8774039/ /pubmed/35052839 http://dx.doi.org/10.3390/biomedicines10010160 Text en © 2022 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 Article
Napolioni, Valerio
Fredericks, Carolyn A.
Kim, Yongha
Channappa, Divya
Khan, Raiyan R.
Kim, Lily H.
Zafar, Faria
Couthouis, Julien
Davidzon, Guido A.
Mormino, Elizabeth C.
Gitler, Aaron D.
Montine, Thomas J.
Schüle, Birgitt
Greicius, Michael D.
Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title_full Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title_fullStr Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title_full_unstemmed Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title_short Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders
title_sort phenotypic heterogeneity among gba p.r202x carriers in lewy body spectrum disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774039/
https://www.ncbi.nlm.nih.gov/pubmed/35052839
http://dx.doi.org/10.3390/biomedicines10010160
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