Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, 34093, Istanbul, Turkey.
Suna and İnan Kıraç Foundation, Neurodegeneration Research Laboratory, KUTTAM, Koç University, School of Medicine, Istanbul, Turkey.
Neurol Sci. 2021 Apr;42(4):1535-1539. doi: 10.1007/s10072-020-04869-6. Epub 2020 Nov 18.
Autosomal recessive cerebellar ataxias are a group of rare neurological diseases with a genetic origin. Recently, the mutations in the PNPLA6 gene were suggested to lead to ataxia and also to other specific syndromes such as Boucher-Neuhauser (ataxia, hypogonadism, and chorioretinal dystrophy) or Gordon-Holmes Syndromes (ataxia, hypogonadism, and brisk reflexes) within a broad spectrum of neurodegenerative diseases. Here we report three patients from a single-family with a novel pathogenic mutation in the PNPLA6 gene which led to predominantly spastic-ataxia, and intractable Holmes tremor. The PNPLA6-related disease should be considered in the differential diagnosis of spastic-ataxias even in the absence of chorioretinal dystrophy, and hypogonadotropic hypogonadism. Further studies should unravel the factors which account for the phenotypic variability present in patients with PNPLA6 gene mutations.
常染色体隐性小脑共济失调是一组罕见的遗传性神经疾病。最近，PNPLA6 基因突变被认为会导致共济失调，也会导致其他特定综合征，如 Boucher-Neuhauser（共济失调、性腺功能减退和脉络膜视网膜营养不良）或 Gordon-Holmes 综合征（共济失调、性腺功能减退和反射亢进），这些综合征属于广泛的神经退行性疾病谱。我们在此报告 3 名来自单一家系的患者，他们携带 PNPLA6 基因的新致病性突变，主要表现为痉挛性共济失调和难治性 Holmes 震颤。即使没有脉络膜视网膜营养不良和促性腺激素低下性性腺功能减退症，PNPLA6 相关性疾病也应在痉挛性共济失调的鉴别诊断中考虑。进一步的研究应该阐明导致 PNPLA6 基因突变患者表型变异的因素。
