INTRODUCTION: Complex forms of spastic paraplegia (SPG) are rare and genetically heterogeneous. In apparently sporadic cases, analysis of known SPG genes often fails to reveal a mutation. METHODS: We report a 24-year-old patient with a syndrome of spastic paraplegia, ataxia, frontotemporal dementia, and lower motor neuron involvement. RESULTS: Screening of the patient's genome for copy number variation identified a novel 276 kb deletion spanning the first exon of the GRID2 gene. MRI scan showed atrophy of the cerebellum, and electromyography revealed a chronic disorder of motor neurons or their axons. A deletion in GRID2, coding for the glutamate receptor delta-2 subunit precursor protein, was excluded in either parent, suggesting that the deletion in the index patient occurred de novo. CONCLUSIONS: We hypothesize that the deletion identified here is the cause of our patient's clinical presentation, due to the resemblance to the GRID2 mutation phenotype in mouse models.
INTRODUCTION: Complex forms of spastic paraplegia (SPG) are rare and genetically heterogeneous. In apparently sporadic cases, analysis of known SPG genes often fails to reveal a mutation. METHODS: We report a 24-year-old patient with a syndrome of spastic paraplegia, ataxia, frontotemporal dementia, and lower motor neuron involvement. RESULTS: Screening of the patient's genome for copy number variation identified a novel 276 kb deletion spanning the first exon of the GRID2 gene. MRI scan showed atrophy of the cerebellum, and electromyography revealed a chronic disorder of motor neurons or their axons. A deletion in GRID2, coding for the glutamate receptor delta-2 subunit precursor protein, was excluded in either parent, suggesting that the deletion in the index patient occurred de novo. CONCLUSIONS: We hypothesize that the deletion identified here is the cause of our patient's clinical presentation, due to the resemblance to the GRID2 mutation phenotype in mouse models.
Authors: Paulo Victor Sgobbi de Souza; Wladimir Bocca Vieira de Rezende Pinto; Gabriel Novaes de Rezende Batistella; Thiago Bortholin; Acary Souza Bulle Oliveira Journal: Cerebellum Date: 2017-04 Impact factor: 3.847
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Authors: Kasper B Hansen; Lonnie P Wollmuth; Derek Bowie; Hiro Furukawa; Frank S Menniti; Alexander I Sobolevsky; Geoffrey T Swanson; Sharon A Swanger; Ingo H Greger; Terunaga Nakagawa; Chris J McBain; Vasanthi Jayaraman; Chian-Ming Low; Mark L Dell'Acqua; Jeffrey S Diamond; Chad R Camp; Riley E Perszyk; Hongjie Yuan; Stephen F Traynelis Journal: Pharmacol Rev Date: 2021-10 Impact factor: 18.923
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