PDF(Pubmed)
Abstract：
Biallelic mutations in the sorbitol dehydrogenase (SORD) gene have been identified as a genetic cause of autosomal recessive axonal Charcot-Marie-Tooth disease 2 (CMT2) and distal hereditary motor neuropathy (dHMN). We herein review the main phenotypes associated with SORD mutations and report the case of a 16-year-old man who was referred to our outpatient clinic for a slowly worsening gait disorder with wasting and weakness of distal lower limbs musculature. Since creatine phosphokinase (CPK) values were persistently raised (1.5fold increased) and a Next-Generation Sequencing CMT-associated panel failed in identifying pathogenic variants, a muscle biopsy was performed with evidence of alterations suggestive of a protein surplus distal myopathy. Finally, Whole-Exome Sequencing (WES) identified two pathogenic SORD variants in the heterozygous state: c.458C > A (p.Ala153Asp) and c.757delG (p.Ala253Glnfs*27). This is an isolated report of compound heterozygosity for two SORD mutations associated with clinical and histological signs of skeletal muscle involvement, expanding the phenotypic expression of SORD mutations.
摘要：
山梨糖醇脱氢酶（SORD）基因的双等位基因突变已被确定为常染色体隐性隐性轴突Charcot-Marie-Tooth病2（CMT2）和远端遗传性运动神经病（dHMN）的遗传原因。我们在此回顾了与SORD突变相关的主要表型，并报告了一名16岁男子因步态障碍缓慢恶化并伴有下肢远端肌肉组织消瘦和无力而被转诊到我们的门诊诊所的病例。由于肌酸磷酸激酶（CPK）值持续升高（增加1.5倍），并且下一代测序CMT相关小组未能鉴定致病变体，进行了肌肉活检，有证据表明蛋白质过剩的远端肌病。最后,全外显子组测序（WES）鉴定出两种处于杂合状态的致病性SORD变体：c.458C>A（p。Ala153Asp）和c.757delG（p。Ala253Glnfs*27)。这是与骨骼肌受累的临床和组织学体征相关的两个SORD突变的复合杂合性的分离报告，扩大SORD突变的表型表达。
