R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome.

TFG (tropomyosin-receptor kinase fused gene) encodes an essential protein in the regulation of vesicular trafficking between endoplasmic reticulum and Golgi apparatus. The homozygous variant c.316C > T within TFG has been previously associated with a complicated hereditary spastic paraplegia (HSP) phenotype in two unrelated Indian families. Here, we describe the first Italian family with two affected siblings harboring the same variant, who in childhood were classified as infantile neuroaxonal dystrophy (INAD) based on clinical and neuropathological findings. Twenty years after the first diagnosis, exome sequencing was instrumental to identify the genetic cause of this disorder and clinical follow-up of patients allowed us to reconstruct the natural history of this clinical entity. Investigations on patient's fibroblasts demonstrate the presence of altered mitochondrial network and inner membrane potential, associated with metabolic impairment. Our study highlights phenotypic heterogeneity characterizing individuals carrying the same pathogenic variant in TFG and provides an insight on tight connection linking mitochondrial efficiency and neuronal health to vesicular trafficking.

Isospin asymmetry in the pseudospin dynamical symmetry.

Pseudospin symmetry in nuclei is investigated considering the Dirac equation with a Lorentz structured Woods-Saxon potential. The isospin correlation of the energy splittings of pseudospin partners with the nuclear potential parameters is studied. We show that, in an isotopic chain, the pseudospin symmetry is better realized for neutrons than for protons. This behavior comes from balance effects among the central nuclear potential parameters. In general, we found an isospin asymmetry of the nuclear pseudospin interaction, opposed to the nuclear spin-orbit interaction which is quasi-isospin symmetric.