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Frequency of GBA Variants in Autopsy‐proven Multiple System Atrophy
Author(s) -
Sklerov Miriam,
Kang Un J.,
Liong Christopher,
Clark Lorraine,
Marder Karen,
Pauciulo Michael,
Nichols William C.,
Chung Wendy K.,
Honig Lawrence S.,
Cortes Etty,
Vonsattel Jean Paul,
Alcalay Roy N.
Publication year - 2017
Publication title -
movement disorders clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 18
ISSN - 2330-1619
DOI - 10.1002/mdc3.12481
Subject(s) - glucocerebrosidase , atrophy , synucleinopathies , autopsy , dementia with lewy bodies , genotype , etiology , pathology , lewy body , dementia , disease , alpha synuclein , medicine , parkinson's disease , gene , biology , genetics
Background Multiple system atrophy ( MSA ) is marked by abnormal inclusions of α‐synuclein in oligodendrogliocytes, and its etiology remains unknown. Variants in the glucocerebrosidase ( GBA ) gene have been associated with the other synucleinopathies, dementia with Lewy bodies, and Parkinson's disease. It is unclear whether glucocerebrosidase variants are associated with MSA . The objective of this study was to analyze the frequency of GBA variants among patients who had autopsy‐proven MSA at a brain bank in New York City. Methods GBA was fully sequenced in brain tissues from 17 patients with autopsy‐proven MSA for whom there was extractable DNA at the Columbia University New York Brain Bank from 2002 to 2016. To test whether brains from patients with MSA were enriched for GBA variants, the frequency of GBA variants in the MSA brains was compared with that of variants in all brains from patients with pure Alzheimer's disease ( AD ) at Columbia University for which GBA genotype was available (n = 82). Results Of 17 MSA brains, 4 carried GBA variants (23.5%), including 1 that was homozygous for N370S and 1 each that carried heterozygous N370S, T369M, and R496H variants. Among the comparator brains with pure AD , 3 of 82 (3.7%) carried GBA variants ( P = 0.0127; Fisher exact test), including 1 each with an N370S homozygous variant, an R496H heterozygous variant, and a T369M heterozygous variant. Conclusion A higher frequency of GBA variants was observed among brains from patients who had pathologically diagnosed MSA compared with the frequency of variants in brains from patients who had AD . The results indicate a need for further investigation into the role of glucocerebrosidase and lysosomal dysfunction in the etiology of MSA .