Rozevska Marija, Rots Dmitrijs, Gailite Linda, Linde Ronalds, Mironovs Stanislavs, Timcenko Maksims, Linovs Viktors, Locmele Dzintra, Micule Ieva, Lace Baiba, Kenina Viktorija
Medical Genetics and Prenatal Diagnostics Clinic, Children's Clinical University Hospital, Riga, Latvia.
Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia.
Front Neurol. 2023 Feb 17;14:1084335. doi: 10.3389/fneur.2023.1084335. eCollection 2023.
HINT1 is an ubiquitous homodimeric purine phosphoramidase belonging to the histidine-triad superfamily. In neurons, HINT1 stabilizes the interaction of different receptors and regulates the effects of their signaling disturbances. Changes in gene are associated with autosomal recessive axonal neuropathy with neuromyotonia. Aim of the study was detailed description of patients' phenotype with homozygous NM_005340.7: c.110G>C (p.Arg37Pro) variant. Seven homozygous and three compound heterozygous patients were recruited and evaluated using standardized tests for CMT patients, in four patients' nerve ultrasonography was performed. The median age of symptom onset was 10 years (range 1-20), with initial complaints being distal lower limb weakness with gait impairment, combined with muscle stiffness, more pronounced in the hands than in the legs and worsened by cold. Arm muscles became involved later, presenting with distal weakness and hypotrophy. Neuromyotonia was present in all reported patients and is thus a diagnostic hallmark. Electrophysiological studies demonstrated axonal polyneuropathy. Impaired mental performance was observed in six out of ten cases. In all patients with neuropathy, ultrasound examination showed significantly reduced muscle volume as well as spontaneous fasciculations and fibrillations. The nerve cross-sectional areas of the median and ulnar nerves were closer to the lower limits of the normal values. None of the investigated nerves had structural changes. Our findings broaden the phenotype of -neuropathy and have implications for diagnostics and ultrasonographic evaluation of -neuropathy patients.
HINT1是一种普遍存在的同二聚体嘌呤磷酸酰胺酶，属于组氨酸三联体超家族。在神经元中，HINT1可稳定不同受体之间的相互作用，并调节其信号紊乱的影响。基因变化与伴有神经肌强直的常染色体隐性轴索性神经病相关。本研究的目的是详细描述携带纯合NM_005340.7:c.110G>C（p.Arg37Pro）变异的患者的表型。招募了7名纯合子和3名复合杂合子患者，并使用针对遗传性运动感觉神经病（CMT）患者的标准化测试进行评估，对4名患者进行了神经超声检查。症状出现的中位年龄为10岁（范围1 - 20岁），最初的主诉是下肢远端无力伴步态障碍，同时伴有肌肉僵硬，手部比腿部更明显，且遇冷会加重。上肢肌肉后来也受累，表现为远端无力和萎缩。所有报告的患者均存在神经肌强直，因此是一个诊断标志。电生理研究显示为轴索性多发性神经病。10例中有6例观察到智力表现受损。在所有患有神经病的患者中，超声检查显示肌肉体积明显减小以及自发束颤和纤颤。正中神经和尺神经的神经横截面积更接近正常值下限。所研究的神经均无结构变化。我们的发现拓宽了神经病的表型，并对神经病患者的诊断和超声评估具有启示意义。
