Mutations in MYO9B are associated with Charcot–Marie–Tooth disease type 2 neuropathies and isolated optic atrophy
European Journal of Neurology · 24 authors, 17 centres
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Whole exome sequencing and targeted sequencing in families with autosomal recessive CMT2 identified novel recessive MYO9B variants in two independent CMT2 families and one isolated optic atrophy case. Functional studies showed that a motor domain variant impairs protein expression and motor activity, and a Myo9b-null mouse exhibited degenerating axons in sciatic and optic nerves.
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All four patients presented with disease onset before age 20 years, progressive distal weakness, bilateral foot drop, reduced or absent sensory action potentials, and intermediate slowing of motor conduction velocities. Functional studies demonstrated that the p.Tyr176His variant, located in the motor domain, had reduced expression in patient fibroblasts and abrogated motor activity in cell-based assays. A Myo9b-null mouse showed degenerating myelinated axons in sciatic and optic nerves. Screening of an optic atrophy cohort identified compound heterozygous MYO9B variants in one patient with isolated optic atrophy.
