Abstract-Text (inkl. Referenzen)

Biallelic SORD mutations were recently identified as a novel cause for autosomal-recessive CMT type 2. Clinically, its associated disease is mainly characterized by progressive distal limb muscle atrophy and weakness. SORD codes for the enzyme sorbitol dehydrogenase, which together with aldose reductase converts glucose to fructose via sorbitol, indicating potential for the study of possible disease specific-treatments such as aldose reductase inhibitors.

We retrospectively screened 166 patients with CMT type 2 without identified genetic etiology by next-generation sequencing and subsequent Sanger sequencing to specifically amplify SORD. Clinical and electrophysiology exam findings were analysed for genotype-phenotype correlation.

Five patients harbored pathogenic SORD mutations (3%) with the most common homozygous pathogenic frameshift variant c.757delG (p.Ala253Glnfs*27) present in four. One case carried this variant and the pathogenic missense variant c.458C>A (p.Ala153Asp) in a compound heterozygous state. Age of onset ranged from early infancy to mid twenties, and clinical and electrophysiological findings comprised signs of slowly progressive distal weakness with predominantly axonal neuropathy in all identified cases.

We confirm SORD mutations as causative for a small subset of prior genetically unresolved axonal CMT in our cohort. Our findings strengthen the importance of screening for SORD mutations in patients with CMT type 2 without identified genetic etiology.