Ciampana Valentina, Corrado Lucia, Magistrelli Luca, Contaldi Elena, Comi Cristoforo, D'Alfonso Sandra, Vecchio Domizia
Neurology Unit, Department of Translational Medicine, Maggiore Della Carità Hospital, University of Piemonte Orientale, 28100 Novara, Italy.
Department of Translational Medicine, Genetic Laboratory, Università del Piemonte Orientale (UPO), 28100 Novara, Italy.
Genes (Basel). 2024 Nov 29;15(12):1556. doi: 10.3390/genes15121556.
BACKGROUND/OBJECTIVES: Axonal Charcot-Marie-Tooth disease type 2 (CMT2) accounts for 24% of Hereditary Motor/Sensory Peripheral Neuropathies. CMT2 type GG, due to four distinct heterozygous mutations in the Golgi brefeldin A resistant guanine nucleotide exchange factor 1 () gene (OMIM 606483), was described in seven cases from four unrelated families with autosomal dominant inheritance. It is characterized by slowly progressive distal muscle weakness and atrophy, primarily affecting the lower limbs. Here, we present two siblings sharing a novel variant.
Patient II.1 (male, 61 years at onset) presented lower limb hypoesthesia and walking difficulty; the examination revealed a postural tremor, a positive Romberg test, and muscle atrophy in the lower limbs and hands. Patient II.2 (his sister, 59 years at onset) had lower limb dysesthesias, hand paresthesia, and lower-limb stiffness. They underwent clinical evaluations, blood tests, and electroneurography. Their father represents a potentially affected individual, although a genetic analysis was not conducted.
All tests for peripheral neuropathies were unremarkable, including metabolic and autoimmune screening. Both showed a mixed demyelinating-axonal sensory-motor neuropathy. Genetic analysis revealed a new heterozygous variant of uncertain significance.
Based on autosomal dominant inheritance, as well as clinical and physiological features, a possible novel CMT2GG was diagnosed. Further research, including functional assays and in vitro studies, is necessary to confirm this variant's causal link.
背景/目的：轴索性2型夏科-马里-图斯病（CMT2）占遗传性运动/感觉性周围神经病的24%。CMT2型GG是由于高尔基体布雷菲德菌素A抗性鸟嘌呤核苷酸交换因子1（）基因（OMIM 606483）中四个不同的杂合突变所致，在四个无关家族的7例常染色体显性遗传病例中被描述。其特征为缓慢进展的远端肌肉无力和萎缩，主要影响下肢。在此，我们报告了一对共享一种新型变异的兄弟姐妹。
患者II.1（男性，发病时61岁）表现为下肢感觉减退和行走困难；检查发现姿势性震颤、闭目难立试验阳性以及下肢和手部肌肉萎缩。患者II.2（其妹妹，发病时59岁）有下肢感觉异常、手部感觉异常和下肢僵硬。他们接受了临床评估、血液检查和神经电生理检查。他们的父亲可能是受累个体，尽管未进行基因分析。
所有周围神经病检查均无异常，包括代谢和自身免疫筛查。两人均表现为脱髓鞘-轴索性感觉运动混合性神经病。基因分析发现一种意义未明的新的杂合变异。
基于常染色体显性遗传以及临床和生理特征，诊断为可能的新型CMT2GG。需要进一步研究，包括功能测定和体外研究，以证实该变异的因果关系。
