Disease relevance of PRX

• Mutations in the Periaxin (PRX) gene are known to cause autosomal recessive demyelinating Charcot-Marie-Tooth (CMT4F) and Dejerine-Sottas disease [1].
• In the field of the peripheral neuropathies we present data on a newly described autosomal recessive Charcot-Marie-Tooth disease (CMT4F) with mutations in the periaxin gene [2].

High impact information on PRX

• In accordance with this, we identified three unrelated Dejerine-Sottas neuropathy patients with recessive PRX mutations-two with compound heterozygous nonsense and frameshift mutations, and one with a homozygous frameshift mutation [3].
• The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin [3].
• The phenotype and locus are different from those of demyelinating CMT4F, recently mapped to 19q13.1-13.3; hence, the disease affecting the Costa Rican family constitutes an axonal, autosomal recessive CMT subtype (ARCMT2B) [4].
• Previous studies have demonstrated that apparent loss-of-function mutations in the periaxin gene cause autosomal recessive Dejerine-Sottas neuropathy or severe demyelinating Charcot-Marie-Tooth disease [5].
• Here, we report a Japanese CMT patient with these characteristic clinical features, who was a compound heterozygote for PRX R1070X and L132FsX153 mutations [6].

Biological context of PRX

• In this report, we extend the associated phenotypes with the identification of two additional families with novel periaxin gene mutations (C715X and R82fsX96) and provide detailed neuropathology [5].

Anatomical context of PRX

• Periaxin (PRX) plays a significant role in the myelination of the peripheral nerve [7].
• Periaxin is involved in connecting myelin to the surrounding basal lamina [8].

References