The work of the Inherited Neuropathies Consortium (INC) have highlighted the involvement of the SORD gene in CMT2:
- they identified 45 people with SORD gene abnormalities with recessive axonal CMT (CMT 2) manifested by muscle weakness and deformities of the feet.
- half of them do not have sensitivity.
- in 69% of cases, it was sporadic.
- in the INC cohort, SORD gene abnormalities are involved in almost 10% of undiagnosed CMT 2 cases, making it one of the most common forms.
The protein SORD (or sorbitol dehydrogenase) takes part in a reaction which transforms sorbitol into fructose.
In cells collected from patients with CMT linked to SORD, the researchers demonstrated an accumulation of sorbitol.
The accumulation of sorbitol also plays a role in neuropathies linked to diabetes.
It is possible to block the production of sorbitol by aldose reductase inhibitors, molecules being studied in diabetic neuropathy. Injected into model CMT2 flies, aldolase reductase inhibitors improve motor deficiency.
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes. Andrea Cortese, Yi Zhu, Adriana P. Rebelo, Sara Negri, Steve Courel, Lisa Abreu, Chelsea J. Bacon, Yunhong Bai, Dana M. Bis-Brewer, Enrico Bugiardini, Elena Buglo, Matt C. Danzi, Shawna M. E. Feely, Alkyoni Athanasiou-Fragkouli, Nourelhoda A. Haridy, Inherited Neuropathy Consortium, Rosario Isasi, Alaa Khan, Matilde Laurà, Stefania Magri, Menelaos Pipis, Chiara Pisciotta, Eric Powell, Alexander M. Rossor, Paola Saveri, Janet E. Sowden, Stefano Tozza, Jana Vandrovcova, Julia Dallman, Elena Grignani, Enrico Marchioni, Steven S. Scherer, Beisha Tang, Zhiqiang Lin, Abdullah Al-Ajmi, Rebecca Schüle, Matthis Synofzik, Thierry Maisonobe, Tanya Stojkovic, Michaela Auer-Grumbach, Mohamed A. Abdelhamed, Sherifa A. Hamed, Ruxu Zhang, Fiore Manganelli, Lucio Santoro, Franco Taroni, Davide Pareyson, Henry Houlden, David N. Herrmann, Mary M. Reilly, Michael E. Shy, R. Grace Zhai & Stephan Zuchner. Nat Genet. 2020 Mai
