Clinical and pathological study of SORD-related distal motor neuropathy caused by novel compound heterozygous mutations in a Chinese patient.

Sorbitol dehydrogenase (SORD) has been identified as the causative gene of autosomal recessive distal hereditary motor neuropathies (dHMN). Here, we describe a 25-year-old woman who presented with progressive weakness of both lower limbs for the previous 10 years. Electrophysiological results suggested only a reduction in the compound muscle action potential (CMAP) amplitude of both the tibial and left deep peroneal nerves and neurogenic changes in needle EMG. A heterozygous c.757delG variant with a splicing c.786 + 1 G>A variant in the SORD gene was identified. A sural nerve biopsy revealed slight axon separation from the myelin sheath and thin myelin sheaths in very few nerve fibres and thickening of the microvasculature basement membrane. Our study expands the pathological and mutation spectrum of the SORD-related neuropathy.

Improving xylitol yield by deletion of endogenous xylitol-assimilating genes: a study of industrial Saccharomyces cerevisiae in fermentation of glucose and xylose.

Engineered Saccharomyces cerevisiae can reduce xylose to xylitol. However, in S.cerevisiae, there are several endogenous enzymes including xylitol dehydrogenase encoded by XYL2, sorbitol dehydrogenases encoded by SOR1/SOR2 and xylulokinase encoded by XKS1 may lead to the assimilation of xylitol. In this study, to increase xylitol accumulation, these genes were separately deleted through CRISPR/Cas9 system. Their effects on xylitol yield of an industrial S. cerevisiae CK17 overexpressing Candida tropicalis XYL1 (encoding xylose reductase) were investigated. Deletion of SOR1/SOR2 or XKS1 increased the xylitol yield in both batch and fed-batch fermentation with different concentrations of glucose and xylose. The analysis of the transcription level of key genes in the mutants during fed-batch fermentation suggests that SOR1/SOR2 are more crucially responsible for xylitol oxidation than XYL2 under the genetic background of S.cerevisiae CK17. The deletion of XKS1 gene could also weaken SOR1/SOR2 expression, thereby increasing the xylitol accumulation. The XKS1-deleted strain CK17ΔXKS1 produced 46.17 g/L of xylitol and reached a xylitol yield of 0.92 g/g during simultaneous saccharification and fermentation (SSF) of pretreated corn stover slurry. Therefore, the deletion of XKS1 gene provides a promising strategy to meet the industrial demands for xylitol production from lignocellulosic biomass.