Peeters Kristien, Chamova Teodora, Tournev Ivailo, Jordanova Albena
Molecular Neurogenomics Group, Department of Molecular Genetics, VIB and University of Antwerp, Antwerpen 2610, Belgium.
Department of Neurology, Medical University-Sofia, Sofia 1431, Bulgaria.
Brain. 2017 Apr 1;140(4):868-877. doi: 10.1093/brain/aww301.
Recessive mutations in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) were recently shown to cause a motor-predominant Charcot-Marie-Tooth neuropathy. About 80% of the patients exhibit neuromyotonia, a striking clinical and electrophysiological hallmark that can help to distinguish this disease and to guide diagnostic screening. HINT1 neuropathy has worldwide distribution and is particularly prevalent in populations inhabiting central and south-eastern Europe. With 12 different mutations identified in more than 60 families, it ranks among the most common subtypes of axonal Charcot-Marie-Tooth neuropathy. This article provides an overview of the present knowledge on HINT1 neuropathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. We propose diagnostic guidelines to recognize and differentiate this entity and suggest treatment strategies to manage common symptoms. As a recent player in the field of hereditary neuropathies, the role of HINT1 in peripheral nerves is unknown and the underlying disease mechanisms are unexplored. We provide a comprehensive overview of the structural and functional characteristics of the HINT1 protein that may guide further studies into the molecular aetiology and treatment strategies of this peculiar Charcot-Marie-Tooth subtype.
编码组氨酸三联体核苷酸结合蛋白1（HINT1）的基因中的隐性突变最近被证明可导致以运动为主的夏科-马里-图斯神经病。约80%的患者表现出神经肌强直，这是一个显著的临床和电生理特征，有助于区分这种疾病并指导诊断筛查。HINT1神经病在全球范围内均有分布，在中欧和东南欧人群中尤为普遍。在60多个家族中已鉴定出12种不同的突变，它是轴索性夏科-马里-图斯神经病最常见的亚型之一。本文概述了目前关于HINT1神经病的知识，旨在提高该领域临床医生和研究人员的认识并激发他们的兴趣。我们提出了诊断指南以识别和区分该疾病实体，并建议了管理常见症状的治疗策略。作为遗传性神经病领域的新成员，HINT1在周围神经中的作用尚不清楚，潜在的疾病机制也未得到探索。我们全面概述了HINT1蛋白的结构和功能特征，这可能会为进一步研究这种特殊的夏科-马里-图斯亚型的分子病因和治疗策略提供指导。
