De novo partial deletion in GRID2 presenting with complicated spastic paraplegia

摘要

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.