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Early‐Onset Parkinsonism Is a Manifestation of the PPP2R5D p. E200K Mutation
Author(s) -
Kim Christine Y.,
Wirth Thomas,
Hubsch Cécile,
Németh Andrea H.,
Okur Volkan,
Anheim Mathieu,
Drouot Nathalie,
Tranchant Christine,
Rudolf Gabrielle,
Chelly Jamel,
TattonBrown Katrina,
Blauwendraat Cornelis,
Vonsattel Jean Paul G.,
Cortes Etty,
Alcalay Roy N.,
Chung Wendy K.
Publication year - 2020
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25863
Subject(s) - parkinsonism , pars compacta , gliosis , substantia nigra , mutation , exome sequencing , neurodevelopmental disorder , medicine , pathology , neuroscience , psychology , biology , genetics , psychiatry , parkinson's disease , disease , autism , gene
PPP2R5D‐ related neurodevelopmental disorder is characterized by a range of neurodevelopmental and behavioral manifestations. We report the association of early‐onset parkinsonism with the PPP2R5D p.E200K mutation. Clinical characterization and exome sequencing were performed on three patients, with postmortem neuropathologic examination for one patient. All patients had mild developmental delay and developed levodopa‐responsive parkinsonism between the ages of 25 and 40 years. The PPP2R5D c.598G>A (p.E200K) mutation was identified in all patients . Neuropathologic examination demonstrated uneven, focally severe neuronal loss and gliosis in the substantia nigra pars compacta, without Lewy bodies. Our findings suggest the PPP2R5D p.E200K mutation to be a possible new cause of early‐onset parkinsonism. ANN NEUROL 2020;88:1028–1033