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.