LRRK2 p.Ile1371Val Mutation in a Case with Neuropathologically Confirmed Multi-System Atrophy

Journal of Parkinson's Disease
Kelsey LeeBirgitt Schüle

Abstract

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. To genetically and pathologically characterize a case with a LRRK2, p.Ile1371Val rare variant and pathologically proven MSA. From the brain donation program at the Parkinson's Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD (n = 20), MSA (n = 4), or PSP (n = 2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases. We identified a known LRRK2, p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was mo...Continue Reading

References

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Citations

May 12, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Giulietta Maria RiboldiSteven Frucht
Apr 23, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Stuart J McCarterWolfgang Singer
Jan 27, 2021·International Journal of Molecular Sciences·Vinita G Chittoor-VinodBirgitt Schüle
Nov 19, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Oihana Errea, Maria Cruz Rodriguez-Oroz
Nov 24, 2020·Frontiers in Neurology·Peggy S EisBirgitt Schüle
Feb 6, 2021·Neurología : publicación oficial de la Sociedad Española de Neurología·G Fernández-PajarínA Castro
Jul 14, 2021·Expert Review of Neurotherapeutics·Luca MarsiliCarlo Colosimo
Oct 7, 2021·Journal of Neural Transmission·David J MarmionJeffrey H Kordower

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Methods Mentioned

BETA
PCR

Software Mentioned

Variant Effect Predictor
GATK

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