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Title:           Genotype and phenotype spectrum of Charcot-Marie-Tooth disease due to mutations in SORD
Subject:         DOI: 10.1093/brain/awaf021; Brain, 148, 10, 2025-02-13.; Abstract: Biallelic loss-of-function mutations in the sorbitol dehydrogenase (SORD) gene cause the most common recessive type of Charcot-Marie-Tooth disease (CMT), CMT-SORD. However, the full genotype-phenotype spectrum and progression of the disease remain to be defined. Notably, a multicentre phase 2/3 study to test the efficacy of govorestat (NCT05397665), a new aldose reductase inhibitor, is currently ongoing. Diagnosing CMT-SORD will become imperative when disease-modifying therapies become available.In this cross-sectional multicentre study, we identified 144 patients from 126 families, including 99 males (69%) and 45 females (31%). Patients represented multiple ancestries, including European, Hispanic, Chinese, Near Eastern and Northern African. We confirmed c.757delG (p.Ala253GlnfsTer27) as the most common pathogenic allele, followed by c.458C>A (p.Ala153Asp), while other variants were identified, mostly in single cases
Keywords:        SORD; natural history; hereditary neuropathy; polyol pathway; aldose reductase
Author:          Andrea Cortese
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        Title: Patients
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        Title: Nerve conduction studies
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        Title: Molecular genetic analyses
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        Title: Genotype spectrum of CMT-SORD
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