Pasanen P, Myllykangas L, Pöyhönen M, Kiuru-Enari S, Tienari P J, Laaksovirta H, Toppila J, Ylikallio E, Tyynismaa H, Auranen M
Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
Acta Neurol Scand. 2016 May;133(5):361-6. doi: 10.1111/ane.12470. Epub 2015 Jul 30.
Mutations in the CHCHD10 gene, which encodes a mitochondrially targeted protein, have emerged as an important cause of motor neuron disease and frontotemporal lobar degeneration. The aim of this study was to assess the clinical variability in a large family carrying the p.Gly66Val mutation of the CHCHD10 gene. This mutation has recently been reported to cause late-onset spinal muscular atrophy (SMAJ) or sensorimotor axonal Charcot-Marie-Tooth neuropathy (CMT2) in the Finnish population.
Nine affected members of an extended Finnish pedigree were included in the study. Detailed clinical and neurophysiological examinations were performed. The CHCHD10 p.Gly66Val mutation was examined by Sanger sequencing.
The heterozygous p.Gly66Val mutation was present in all affected individuals from whom a DNA sample was available. The clinical phenotype varied from proximal sensorimotor neuropathy to spinal muscular atrophy and in one case resembled motor neuron disease ALS at its early stages. The age of onset varied from 30 to 73 years.
Our data demonstrate that even within the same family, the p.Gly66Val variant can cause variable phenotypes ranging from CMT2-type axonal neuropathy to spinal muscular atrophy, which may also present as an ALS-like disease. The spectrum of CHCHD10-related neuromuscular disease has widened rapidly, and we recommend keeping the threshold for genetic testing low particularly when dominant inheritance or mitochondrial pathology is present.
编码线粒体靶向蛋白的CHCHD10基因突变已成为运动神经元病和额颞叶变性的重要病因。本研究旨在评估一个携带CHCHD10基因p.Gly66Val突变的大家庭中的临床变异性。最近有报道称，该突变在芬兰人群中可导致迟发性脊髓性肌萎缩症（SMAJ）或感觉运动轴索性夏科-马里-图斯神经病变（CMT2）。
本研究纳入了一个芬兰大家庭中的9名受影响成员。进行了详细的临床和神经生理学检查。通过桑格测序检测CHCHD10基因的p.Gly66Val突变。
在所有可获取DNA样本的受影响个体中均存在杂合的p.Gly66Val突变。临床表型从近端感觉运动神经病变到脊髓性肌萎缩症不等，其中1例在疾病早期类似于运动神经元病肌萎缩侧索硬化症。发病年龄在30至73岁之间。
我们的数据表明，即使在同一家族中，p.Gly66Val变异也可导致从CMT2型轴索性神经病变到脊髓性肌萎缩症等多种不同表型，后者也可能表现为类似肌萎缩侧索硬化症的疾病。CHCHD10相关神经肌肉疾病的范围迅速扩大，我们建议尤其在存在显性遗传或线粒体病理的情况下，降低基因检测的阈值。
