PP09.10 – 2510: A novel case of periaxin-related neuropathy associated with cataract: Expanding the clinical and molecular spectrum of perxiaxin mutation

Abstract

Objective Periaxin gene (PRX) is responsible for autosomal recessive early onset demyelinlating neuropathy: Charcot-Marie Tooth disease 4F (CMT4F) or its severe form Dejerine Sottas neuropathy (DSN). Periaxin protein is essential for maintenance of the peripheral nerve myelin probably in stabilizing its structure. It also functions as a scaffold protein that plays a role in lens membrane organization and cell adhesive interactions. Methods Exome sequencing. Results This report describes a child of non-consanguineous healthy parents with delayed motor milestones, frequent falls, and subcapsular cataract. His neurological exam revealed typical neuropathic features of the lower extremities: weakness of the lower limbs accompanied by absence of deep tendon reflexes. There was no sensory deficiency though he walked on abroad basis. Even so, his motor functions have improved over the years. Nerve conduction velocity (NCV) demonstrated demyelinating process with secondary axonal damage. Bilateral sub capsular cataract was discovered at one year old with no other ophthalmic pathology. A novel homozygote frame shift mutation c.418-419insG (P.m 149 fs) in the PRX gene was identified by whole exome sequencing and was confirmed by molecular analysis. Both his parents were found to be heterozygote carriers of this mutation. Conclusion Mutation in the periaxin protein is most probably the cause of peripheral distal neuropathy and cataract in this child. As of today, cataracts caused by mutations in the PRX gene were demonstrated only in laboratory animals. This is the first description of human congenital neuropathy coexistence with congenital cataract caused by mutations in the PRX gene. This is a new clinical presentation of PRX related hereditary neuropathy. It is suggested that careful eye examination should be done in every patients with congenital neuropathy. The coexistence of neuropathy and cataract may direct to the final diagnosis and its genetic cause.