三代患有脱髓鞘型夏科-马里-图斯病的佛蒙特人身上发现的新型髓磷脂蛋白零突变
Novel Myelin Protein Zero Mutation in 3 Generations of Vermonters With Demyelinating Charcot-Marie-Tooth Disease.
作者信息
Lorance David K, Mandigo Kelly A, Hehir Michael K
机构信息
Department of Neurological Sciences, University of Vermont, Burlington, VT.
出版信息
J Clin Neuromuscul Dis. 2018 Mar;19(3):101-107. doi: 10.1097/CND.0000000000000188.
OBJECTIVES
We report the clinical phenotype in 3 consecutive generations with demyelinating Charcot-Marie-Tooth disease that possess a novel sequence variant of myelin protein zero (MPZ).
METHODS
Family members from 3 consecutive generations were interviewed, examined, and studied with electrodiagnostic testing. Commercially available next-generation sequencing was performed for the proband. Single-gene analysis was performed for the remaining family members.
RESULTS
All patients demonstrated symmetric distal weakness; symmetric distal sensory loss; and diminished deep tendon reflexes. Electrodiagnostic testing was consistent with primary distal demyelination with secondary axon loss. Genetic testing identified a novel base-pair substitution of MPZ (c.314C>T), resulting in a missense variant (p.Pro105Leu).
CONCLUSIONS
The novel MPZ base-pair substitution in this family is associated with inherited distal demyelinating neuropathy and should be reclassified as pathogenic for Charcot-Marie-Tooth.
目的
我们报告了连续三代患有脱髓鞘型夏科-马里-图斯病（Charcot-Marie-Tooth disease）的临床表型，这些患者存在髓鞘蛋白零（MPZ）的一种新序列变异。
方法
对连续三代的家庭成员进行访谈、检查，并进行电诊断测试研究。对先证者进行了商用下一代测序。对其余家庭成员进行了单基因分析。
结果
所有患者均表现为对称性远端肌无力；对称性远端感觉丧失；以及深部腱反射减弱。电诊断测试结果与原发性远端脱髓鞘伴继发性轴突丢失一致。基因检测发现MPZ有一个新的碱基对替换（c.314C>T），导致错义变异（p.Pro105Leu）。
结论
该家族中MPZ新的碱基对替换与遗传性远端脱髓鞘性神经病相关，应重新分类为夏科-马里-图斯病的致病因素。
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