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Article

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

by
Valerio Napolioni
1,*,
Carolyn A. Fredericks
1,
Yongha Kim
1,
Divya Channappa
2,
Raiyan R. Khan
1,
Lily H. Kim
1,
Faria Zafar
2,
Julien Couthouis
3,
Guido A. Davidzon
4,
Elizabeth C. Mormino
1,
Aaron D. Gitler
3,
Thomas J. Montine
2,
Birgitt Schüle
2,† and
Michael D. Greicius
1,†
1
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
2
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
3
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
4
Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biomedicines 2022, 10(1), 160; https://doi.org/10.3390/biomedicines10010160
Submission received: 9 November 2021 / Revised: 3 January 2022 / Accepted: 11 January 2022 / Published: 12 January 2022
(This article belongs to the Special Issue Biomarkers in Neurodegenerative Diseases 2.0)
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Abstract

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.
Keywords: Gaucher’s disease; glucocerebrosidase; genetics; Lewy body dementia; mutation; neuropathology; Parkinson’s disease; sequencing Gaucher’s disease; glucocerebrosidase; genetics; Lewy body dementia; mutation; neuropathology; Parkinson’s disease; sequencing

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MDPI and ACS Style

Napolioni, V.; Fredericks, C.A.; Kim, Y.; Channappa, D.; Khan, R.R.; Kim, L.H.; Zafar, F.; Couthouis, J.; Davidzon, G.A.; Mormino, E.C.; et al. Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders. Biomedicines 2022, 10, 160. https://doi.org/10.3390/biomedicines10010160

AMA Style

Napolioni V, Fredericks CA, Kim Y, Channappa D, Khan RR, Kim LH, Zafar F, Couthouis J, Davidzon GA, Mormino EC, et al. Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders. Biomedicines. 2022; 10(1):160. https://doi.org/10.3390/biomedicines10010160

Chicago/Turabian Style

Napolioni, Valerio, Carolyn A. Fredericks, Yongha Kim, Divya Channappa, Raiyan R. Khan, Lily H. Kim, Faria Zafar, Julien Couthouis, Guido A. Davidzon, Elizabeth C. Mormino, and et al. 2022. "Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders" Biomedicines 10, no. 1: 160. https://doi.org/10.3390/biomedicines10010160

APA Style

Napolioni, V., Fredericks, C. A., Kim, Y., Channappa, D., Khan, R. R., Kim, L. H., Zafar, F., Couthouis, J., Davidzon, G. A., Mormino, E. C., Gitler, A. D., Montine, T. J., Schüle, B., & Greicius, M. D. (2022). Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders. Biomedicines, 10(1), 160. https://doi.org/10.3390/biomedicines10010160

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