Hereditary motor sensory neuropathy with proximal involvement (HMSN‐P) associated with TFG p.Pro285Leu variant in an Italian family with a motor neuron disease‐like clinical picture.

This article focuses on the association of Tropomyosin-receptor kinase fused gene (TFG) variants, particularly the p.Pro285Leu substitution, with hereditary motor sensory neuropathy with proximal involvement (HMSN-P), a rare neuronopathy characterized by progressive proximal muscle weakness and fasciculations. The study reports a European family presenting an atypical motor neuron disease (MND)-like phenotype linked to the TFG p.Pro285Leu variant, expanding the known geographic and ethnic distribution beyond previously reported Asian cases. Clinical, electrophysiological, and pathological findings indicate overlap between HMSN-P and MNDs, including shared pathogenic mechanisms involving disruption of the ubiquitin-proteasome system and vesicle trafficking. The authors suggest that TFG should be included in next-generation sequencing (NGS) panels for patients with atypical MND presentations.