Utility of whole exome sequencing in evaluation of juvenile motor neuron disease

Muscle & Nerve
Sonika AgarwalTimothy E Lotze

Abstract

This case report focuses on identifying novel mutations in juvenile motor neuron disease and emphasizes the significance of whole exome sequencing (WES). We report a 13-year-old Hispanic boy with rapidly progressive weakness, muscle atrophy, tremor, and tongue fasciculation, along with upper motor neuron findings of hyperactive gag reflex, hyperreflexia, and cog-wheel rigidity. Electromyography was suggestive of motor neuron disease. After an extensive evaluation, WES was performed. WES identified a heterozygous de novo variant of unknown clinical significance (VUS) in the fused-in-sarcoma gene (FUS) [c.1554_1557del]. Although initially reported as a VUS, the clinical data from our patient and data from the medical literature support that the variant is indeed disease-causing. The genetic etiology of amyotrophic lateral sclerosis (ALS) is heterogeneous and, as clinical sequencing for FUS was not available, WES was the only method by which a diagnosis of juvenile ALS could be made.

References

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Citations

Apr 14, 2020·Journal of Child Neurology·Vincent Picher-MartelNicolas Chrestian
Jul 19, 2017·Molecular Genetics & Genomic Medicine·Fleur C GartonPamela A McCombe
Nov 21, 2017·Biological Reviews of the Cambridge Philosophical Society·Zi-Bing JinJinyu Wu
Nov 28, 2018·Acta Neuropathologica·Gaël Nicolas, Joris A Veltman
Jan 9, 2019·Frontiers in Neurology·Yun PengHong Jiang

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