de Vries R J, Jaeger B, Hellebrekers D M E I, Reneman L, Verhamme C, Smeets H J M, van Maarle M C, de Visser M, Bleeker F E
Department of Clinical Genetics, Amsterdam University Medical Center, location Academic Medical Center, Amsterdam, The Netherlands.
Department of Neurology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands.
Clin Neurol Neurosurg. 2021 Jul;206:106637. doi: 10.1016/j.clineuro.2021.106637. Epub 2021 Apr 20.
Variants of the C19ORF12-gene have been described in patients with spastic paraplegia type 43 and in patients with mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration associated with brain iron accumulation (NBIA). In both subtypes optic atrophy and neuropathy have been frequently described. This case report describes a patient with bilateral optic atrophy and severe distal muscle weakness based on motor neuropathy without involvement of the central nervous system. Exome sequencing revealed a homozygous pathogenic missense variant (c.187G>C;p.Ala63Pro) of the C19ORF12-gene while iron deposits were absent on repeat MR-imaging of the brain, thus showing that peripheral neuropathy and optic neuropathy can be the sole manifestations of the C19ORF12-related disease spectrum whereby iron accumulation in the brain may be absent.
在43型痉挛性截瘫患者以及线粒体膜蛋白相关神经变性（MPAN）患者中已发现C19ORF12基因的变异，MPAN是一种与脑铁沉积（NBIA）相关的神经变性亚型。在这两种亚型中，经常会出现视神经萎缩和神经病变。本病例报告描述了一名患者，该患者双侧视神经萎缩，基于运动神经病变出现严重的远端肌肉无力，但未累及中枢神经系统。外显子组测序显示C19ORF12基因存在纯合致病性错义变异（c.187G>C；p.Ala63Pro），而脑部重复磁共振成像未发现铁沉积，这表明周围神经病变和视神经病变可能是C19ORF12相关疾病谱的唯一表现形式，而脑部可能不存在铁沉积。
