PLEKHG5-related autosomal recessive lower motor neuron disease with dysmyelination in peripheral nerves.

Objective Pleckstrin homology domain-containing family G member 5 (PLEKHG5) is a nuclear factor-κ-B-activator gene that predominantly expresses in the neurons and Schwann cells of the peripheral nervous system. Variations in the PLEKHG5 have shown an intermediate form of autosomal recessive Charcot-Marie-Tooth disease and lower motor neuron disease in childhood. Materials and methods This study investigated clinically, electrophysiologically, genetically, and pathologically a young girl with lower motor neuron disease who had weakness and wasting of all limbs starting in early childhood. Results Next-generation sequencing found a novel compound heterozygous missense variation c.2038-1G>A and c.1219G>T of PLEKHG5 gene. Electromyography revealed a neurogenic pattern, and nerve conduction study indicated subclinical sensory neuropathy. Sural biopsy showed hypomyelination, hypermyelination, and infolding myelin membranes coiled into the myelinated axon. Conclusion This study identifies, pathologically, novel compound heterozygous mutations and phenotype in PLEKHG5-related lower motor neuron disease and dysmyelination in a patient with PLEKHG5 mutation.