De novo partial deletion in GRID2 presenting with complicated spastic paraplegia.

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.