Continuum of phenotypes in hereditary motor and sensory neuropathy with proximal predominance and Charcot–Marie–Tooth patients with TFG mutation

Charcot–Marie–Tooth (CMT) is a common neuropathy, and hereditary motor and sensory neuropathy with proximal predominance (HMSN‐P) is a recently described rare neuromuscular disease. Although many genes have been implicated for CMT, TFG is the only known HMSN‐P‐causing gene. Within the framework of diagnostic criteria, clinical variation is evident among CMT‐diagnosed and also HMSN‐P‐diagnosed individuals. Mutations that cause p.(Pro285Leu) and p.(Gly269Val) in TFG were earlier reported as cause of HMSN‐P in two Iranian pedigrees. Here, we report the identification of p.(Gly269Val) in TFG as cause of CMT in a large Iranian pedigree. The clinical features of patients of the three pedigrees are presented and critically compared. Similarities between the two HMSN‐P‐diagnosed pedigrees with different TFG mutations, and differences between the two differentially diagnosed pedigrees with the same p.(Gly269Val) mutation were evident. The clinical features of the HMSN‐P pedigree with the p.(Pro285Leu) and the CMT pedigree with the p.(Gly269Val) mutation were clearly congruent with the respective diagnoses, whereas the features of the HMSN‐P‐diagnosed pedigree with the p.(Gly269Val) were intermediate between the other two pedigrees. It is therefore suggested that the clinical features of the three Iranian pedigrees with TFG mutations and diagnosed with HMSN‐P or CMT represent a continuum.