通过报告一种新型变体 c.210T>G 和亚临床肌肉受累的证据,扩展了 SORD 相关周围神经病变的遗传和临床范围

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY
Lu Li, Yongzhi Xie, Sen Zeng, Xiaobo Li, Zhiqiang Lin, Shunxiang Huang, Huadong Zhao, Wanqian Cao, Lei Liu, Jun Liu, Pengfei Rong, Ruxu Zhang
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引用次数: 0

摘要

背景和目的 已发现山梨醇脱氢酶(SORD)基因的双叶变体是常染色体隐性(AR)周围神经病(PN)的遗传病因,表现为夏科-玛丽-牙病 2 型(CMT2)或远端遗传性运动神经病(dHMN)。我们的目的是观察一组 SORD 相关 PN(SORD-PN)患者的遗传和临床谱系。 方法 共有 107 名 AR 或散发性 CMT2/dHMN 患者接受了全外显子组测序的分子诊断和随后的 Sanger 测序验证。收集并分析了 SORD-PN 的表型数据。 结果 107 例患者中有 11 例(10.28%)被确定为 SORD-PN,其中包括 4 例 CMT2 患者和 7 例 dHMN 患者。F-d3 中的 SORD 变异 c.210 T > G;p.His70Gln 最早被报道,随后的分析表明该变异导致 SORD 酶功能丧失。在 SORD-PN 患者中经常发现亚临床肌肉受累的证据,包括 10 例患者血清肌酸激酶(CK)水平轻度至中度升高,1 例患者出现肌源性电生理改变,5 例患者在接受下肢核磁共振成像检查时出现肌肉水肿。SORD-PN 患者的空腹血清山梨醇水平(9.69 ± 1.07 mg/L)是健康杂合子受试者(0.11 ± 0.01 mg/L)的 88 倍,是健康对照组(0.07 ± 0.02 mg/L)的 138 倍。 解释 发现了新型 SORD 变异 c.210 T > G;p.His70Gln 和亚临床肌肉受累的证据,这扩大了 SORD-PN 的遗传和临床范围。亚临床肌肉受累可能是一种常见但容易被忽视的临床特征。随访队列研究证实,血清肌酸激酶和空腹血清山梨醇水平有望成为敏感的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expanding the genetic and clinical spectrum of SORD-related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement

Background and Aims

Biallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot–Marie–Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD-related PN (SORD-PN).

Methods

A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole-exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD-PN were collected and analyzed.

Results

Eleven (10.28%) of 107 patients were identified as SORD-PN, including four with CMT2 and seven with dHMN. The SORD variant c.210 T > G;p.His70Gln in F-d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD-PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in one patient, and muscle edema in five patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88-fold higher in SORD-PN patients (9.69 ± 1.07 mg/L) than in healthy heterozygous subjects (0.11 ± 0.01 mg/L) and 138-fold higher than in healthy controls (0.07 ± 0.02 mg/L).

Interpretation

The novel SORD variant c.210 T > G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD-PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow-up cohort study.

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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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