Jiang Nan, Vazquez Do Campo Rocio, Kazamel Mohamed
Division of Neuromuscular Disease, Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL, United States.
Front Neurol. 2023 Feb 6;14:1007051. doi: 10.3389/fneur.2023.1007051. eCollection 2023.
Recessive mutations in the gene encoding the histidine triad nucleotide-binding protein 1 (HINT1) are associated with axonal motor-predominant Charcot-Marie-Tooth (CMT) disease with neuromyotonia. A total of 24 gene mutations have been reported so far. Some of these cases had mild to moderate elevations of creatinine kinase with no earlier reports of muscle biopsy findings in these cases. In this study, we describe a patient with axonal motor-predominant neuropathy and myopathy with rimmed vacuoles, likely due to a novel gene mutation.
A 35-year-old African American man presented with insidious onset and progressive symmetric distal leg weakness followed by hand muscle atrophy and weakness since the age of 25. He had no muscle cramps or sensory complaints. His 38-year-old brother developed similar symptoms beginning in his early 30 s. On neurologic examination, the patient had distal weakness and atrophy in all limbs, claw hands, pes cavus, absent Achilles reflexes, and normal sensory examination. Electrodiagnostic studies revealed absent/reduced compound motor action potential amplitudes distally with normal sensory responses with no neuromyotonia. His sural nerve biopsy showed a chronic non-specific axonal neuropathy, and a biopsy of the tibialis anterior muscle demonstrated myopathic features and several muscle fibers harboring rimmed vacuoles without inflammation in addition to chronic denervation changes. A homozygous variant, p.I63N (c.188T > A), in the gene was found in both brothers.
We describe a novel, likely pathogenic, pI63N (c.188T > A) homozygous variant associated with hereditary axonal motor-predominant neuropathy without neuromyotonia in two African American brothers. The presence of rimmed vacuoles on muscle biopsy raises the possibility that mutations in the gene may also cause myopathy.
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与伴有神经肌强直的轴索性运动为主型夏科-马里-图斯病（CMT）相关。迄今为止，共报道了24种基因突变。其中一些病例的肌酸激酶有轻度至中度升高，且此前尚无这些病例肌肉活检结果的报道。在本研究中，我们描述了一名可能因新的基因突变而患有轴索性运动为主型神经病变和伴有镶边空泡的肌病的患者。
一名35岁的非裔美国男性自25岁起出现隐匿起病、进行性对称性下肢远端无力，随后出现手部肌肉萎缩和无力。他没有肌肉痉挛或感觉异常。他38岁的哥哥在30岁出头时也出现了类似症状。神经系统检查发现，该患者四肢均有远端无力和萎缩、爪形手、高弓足、跟腱反射消失，感觉检查正常。电诊断研究显示，远端复合运动动作电位波幅缺失/降低，感觉反应正常，无神经肌强直。他的腓肠神经活检显示为慢性非特异性轴索性神经病变，胫前肌活检显示有肌病特征，除慢性失神经改变外，还有几根肌肉纤维含有镶边空泡且无炎症。在两兄弟中均发现该基因的纯合变异p.I63N（c.188T > A）。
我们描述了一种新的、可能致病的pI63N（c.188T > A）纯合变异，它与两名非裔美国兄弟的遗传性轴索性运动为主型神经病变相关，且无神经肌强直。肌肉活检中镶边空泡的存在提示该基因的突变也可能导致肌病。
