Mitogen-activated protein kinase 8-interacting protein 3 gene (MAPK8IP3) encodes the
c-Jun-amino-terminal kinase-interacting protein 3 (JIP3) and is involved in retrograde
axonal transport. Heterozygous de novo pathogenic variants in MAPK8IP3 result in a
neurodevelopmental disorder with or without brain abnormalities and possible axonal
peripheral neuropathy. Whole-exome sequencing was performed on an individual presenting
with severe congenital muscle hypotonia of neuronal origin mimicking lethal spinal
muscular atrophy. Compound heterozygous rare variants (a splice and a missense) were
detected in MAPK8IP3, inherited from the healthy parents. Western blot analysis in
a muscle biopsy sample showed a more than 60% decrease in JIP3 expression. Here, we
suggest a novel autosomal recessive phenotype of a lower motor neuron disease caused
by JIP3 deficiency.
