Novel TFG mutation causes autosomal-dominant spastic paraplegia and defects in autophagy

Mutations in the tropomyosin receptor kinase fused (TFG) have been identified as contributing to several neurological disorders: hereditary spastic paraplegia (HSP), hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P), and Charcot-Marie-Tooth disease type 2 (CMT2). Here, we describe a novel heterozygous TFG variant (p.R42Q) responsible for pure HSP. We have further confirmed that the well-documented, recessively inherited spastic paraplegia, previously attributed to homozygous TFG mutations, also exists in a dominantly inherited form. Notably, despite the distinct clinical features and muscle pathologies between HSP and HMSN-P patients, shared cellular phenotypes across different clinical manifestations caused by TFG mutations were observed. Our research suggests that targeting autophagy may facilitate the development of a uniform treatment for TFG-related neurological disorders. (By Dr. Ling Xu, https://jmg.bmj.com/content/61/4/325 )

Dr. Ling Xu (left) and Professor Pengfei Lin (right)

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