A compound heterozygous pathogenic variant in b4galnt1 is associated with axonal charcot-marie-tooth disease

Background and Purpose Pathogenic variants in B4GALNT1 have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-Tooth disease (CMT). Methods Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line. Results The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in B4GALNT1 as the causative of the present patient, a 53-year-old male who pre-sented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. B4GALNT1 was crit-ical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of B4GALNT1. Conclusions This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in B4GALNT1. This finding expands the clinical and genetic spectra of peripheral neuropathy.