Abstract：
Pathogenic, biallelic variants in SORD were identified in 2020 as a novel cause for autosomal-recessive Charcot-Marie-Tooth disease (CMT) type 2, an inherited neuropathy. SORD codes for the enzyme sorbitol dehydrogenase. Loss of this enzyme\'s activity leads to an increase of sorbitol in serum. We retrospectively screened 166 patients with axonal neuropathy (predominantly CMT type 2, but including intermediate form of CMT and distal hereditary motor neuropathy (dHMN)) without identified genetic etiology for SORD mutations at a single large German neuromuscular center. Clinical and electrophysiology exam findings were analyzed for genotype-phenotype correlation. Five patients of the total cohort of 166 patients harbored pathogenic variants in SORD (3%). The homozygous frameshift variant c.757delG (p.Ala253Glnfs*27) was the most common (4/5). One additional case carried this variant on one allele only and an additional pathogenic missense variant c.458C > A (p.Ala153Asp) on the other allele. Age of onset ranged from early infancy to mid-twenties, and phenotypes comprised axonal CMT (4) and dHMN (1). Our findings strengthen the importance of screening for pathogenic variants in SORD, especially in patients with genetically unconfirmed axonal neuropathy, especially CMT type 2 and dHMN.
摘要：
致病性，SORD的双等位基因变异体于2020年被确定为常染色体隐性遗传性Charcot-Marie-Tooth病(CMT)2型遗传性神经病变的新病因.SORD编码山梨糖醇脱氢酶。这种酶活性的丧失导致血清中山梨糖醇的增加。我们回顾性筛选了166例轴索神经病（主要是CMT2型，但包括中间型CMT和远端遗传性运动神经病（dHMN））患者，但未在单个大型德国神经肌肉中心确定SORD突变的遗传病因。分析临床和电生理检查结果的基因型-表型相关性。166名患者的队列中有5名患者携带SORD的致病变异（3％）。纯合移码变体c.757delG（p。Ala253Glnfs*27）是最常见的（4/5）。另一个病例仅在一个等位基因上携带该变体，另一个致病性错义变体c.458C>A（p。Ala153Asp)上的其他等位基因。发病年龄从婴儿早期到二十多岁，表型包括轴突CMT(4)和dHMN(1)。我们的发现加强了在SORD中筛查致病变异的重要性，尤其是在遗传未确诊的轴索神经病患者中，特别是2型CMT和dHMN。
