García-Sobrino Tania, Blanco-Arias Patricia, Palau Francesc, Espinós Carmen, Ramirez Laura, Estela Anna, San Millán Beatriz, Arias Manuel, Sobrido María-Jesús, Pardo Julio
Department of Neurology, Hospital Clínico, Santiago de Compostela, Spain; Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain.
Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
Neuromuscul Disord. 2017 Jul;27(7):667-672. doi: 10.1016/j.nmd.2017.01.008. Epub 2017 Jan 17.
There are few reports on axonal CMT due to dominant GDAP1 mutations. We describe two unrelated Spanish families with a dominant axonal CMT. A novel in frame GAA deletion in exon 5 of the GDAP1 gene (c.677_679del; p.R226del) was identified in both families. Disease onset varied from early childhood to adulthood. Affected family members complained of distal lower limb weakness, cramps and foot deformities with variable CMTNS score in both families. Several individuals were asymptomatic or had paraesthesia only, however neurological examination and nerve conduction studies demonstrated neuropathic signs. Transfection of HeLa cells with the p.R226del mutation led to an increased mitochondrial aggregation. We report an AD-CMT2K with large phenotypic variability due to a novel dominant GDAP1 variant. This is the second founder GDAP1 pathogenic variant reported in Spain.
关于由显性GDAP1突变导致的轴索性遗传性运动感觉神经病（CMT）的报道较少。我们描述了两个无关的西班牙家族，他们患有显性轴索性CMT。在这两个家族中均鉴定出GDAP1基因第5外显子中的一个新的框内GAA缺失（c.677_679del；p.R226del）。发病年龄从幼儿期到成年期不等。两个家族中受影响的家庭成员均主诉下肢远端无力、痉挛和足部畸形，CMT神经病变评分各异。有几个个体无症状或仅有感觉异常，然而神经学检查和神经传导研究显示有神经病变体征。用p.R226del突变转染HeLa细胞导致线粒体聚集增加。我们报告了一种由于新型显性GDAP1变异而具有大表型变异性的常染色体显性遗传CMT2K。这是西班牙报道的第二个GDAP1致病奠基者变异。
