Seelen Meinie, Visser Anne E, Overste Daniel J, Kim Hong J, Palud A, Wong Tsz H, van Swieten John C, Scheltens Philip, Voermans Nicol C, Baas Frank, de Jong J M B V, van der Kooi Anneke J, de Visser Marianne, Veldink Jan H, Taylor J Paul, Van Es Michael A, van den Berg Leonard H
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
Neurobiol Aging. 2014 Aug;35(8):1956.e9-1956.e11. doi: 10.1016/j.neurobiolaging.2014.01.152. Epub 2014 Feb 6.
Inclusion body myopathy (IBM) associated with Paget disease of the bone, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), sometimes called IBMPFD/ALS or multi system proteinopathy, is a rare, autosomal dominant disorder characterized by progressive degeneration of muscle, brain, motor neurons, and bone with prominent TDP-43 pathology. Recently, 2 novel genes for multi system proteinopathy were discovered; heterogenous nuclear ribonucleoprotein (hnRNP) A1 and A2B1. Subsequently, a mutation in hnRNPA1 was also identified in a pedigree with autosomal dominant familial ALS. The genetic evidence for ALS and other neurodegenerative diseases is still insufficient. We therefore sequenced the prion-like domain of these genes in 135 familial ALS, 1084 sporadic ALS, 68 familial FTD, 74 sporadic FTD, and 31 sporadic IBM patients in a Dutch population. We did not identify any mutations in these genes in our cohorts. Mutations in hnRNPA1 and hnRNPA2B1 prove to be a rare cause of ALS, FTD, and IBM in the Netherlands.
伴有骨佩吉特病、额颞叶痴呆（FTD）和肌萎缩侧索硬化症（ALS）的包涵体肌病（IBM），有时称为IBMPFD/ALS或多系统蛋白病，是一种罕见的常染色体显性疾病，其特征为肌肉、脑、运动神经元和骨骼进行性退化，并伴有显著的TDP-43病理改变。最近，发现了两个与多系统蛋白病相关的新基因；异质性核糖核蛋白（hnRNP）A1和A2B1。随后，在一个常染色体显性家族性ALS家系中也鉴定出hnRNPA1的突变。ALS和其他神经退行性疾病的遗传证据仍然不足。因此，我们对荷兰人群中的135例家族性ALS、1084例散发性ALS、68例家族性FTD、74例散发性FTD和31例散发性IBM患者的这些基因的朊病毒样结构域进行了测序。我们在我们的队列中未发现这些基因的任何突变。在荷兰，hnRNPA1和hnRNPA2B1的突变被证明是ALS、FTD和IBM的罕见病因。
