Svenstrup Kirsten, Nielsen Troels Tolstrup, Aidt Frederik, Rostgaard Nina, Duno Morten, Wibrand Flemming, Vinther-Jensen Tua, Law Ian, Vissing John, Roos Peter, Hjermind Lena Elisabeth, Nielsen Jørgen Erik
Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Cerebellum. 2017 Feb;16(1):62-67. doi: 10.1007/s12311-016-0765-1.
The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well.
脊髓小脑共济失调（SCA）是一组罕见的遗传性神经退行性疾病，其特征为缓慢进展的小脑共济失调，导致步态不稳、动作笨拙和构音障碍。这些疾病主要以常染色体显性方式遗传。先前已证明，编码线粒体m-AAA蛋白酶亚基的AFG3L2基因突变会导致28型脊髓小脑共济失调（SCA28）。在此，我们展示了来自一个常染色体显性小脑共济失调家族的三名患者的临床表型，并通过分子遗传学和计算机模拟表明，这是由AFG3L2基因中的一种新型错义突变引起的。此外，我们首次展示了SCA28患者的脑部氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）以及骨骼肌的选择性I型纤维萎缩，这表明SCA28也累及非神经系统。
