Kiiski K.,University of Helsinki |
Laari L.,University of Helsinki |
Lehtokari V.-L.,University of Helsinki |
Lunkka-Hytonen M.,University of Helsinki |
And 5 more authors.
Neuromuscular Disorders | Year: 2013
Nemaline myopathy (NM) constitutes a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of recessively inherited NM. NEB is one of the most largest genes in human. To date, 68 NEB mutations, mainly small deletions or point mutations have been published. The only large mutation characterized is the 2.5. kb deletion of exon 55 in the Ashkenazi Jewish population. To investigate any copy number variations in this enormous gene, we designed a novel custom comparative genomic hybridization microarray, NM-CGH, targeted towards the seven known genes causative for NM. During the validation of the NM-CGH array we identified two novel deletions in two different families. The first is the largest deletion characterized in NEB to date, (∼53. kb) encompassing 24 exons. The second deletion (1. kb) covers two exons. In both families, the copy number change was the second mutation to be characterized and shown to have been inherited from one of the healthy carrier parents. In addition to these novel mutations, copy number variation was identified in four samples in three families in the triplicate region of NEB. We conclude that this method appears promising for the detection of copy number variations in NEB. © 2012 Elsevier B.V..
Antonini A.,IRCSS San Camillo
Neuropsychiatric Disease and Treatment | Year: 2011
Immediate-release (IR) pramipexole is indicated for the symptomatic treatment of idiopathic Parkinson's disease (PD), either alone (without levodopa) or in combination with levodopa, that is, during the entire progress of disease up to the advanced stage. It is also currently indicated for the treatment of moderate-to-severe primary restless legs syndrome (RLS). An extended-release (ER) formulation of pramipexole has been developed to allow a once-daily formulation and to provide more stable dopaminergic stimulation. This review summarized the pharmacokinetic profile of pramipexole for both the IR and ER formulations, and discussed the role of pramipexole in the management of early and advanced PD. The introduction of a once-daily formulation of pramipexole poses significant potential advantages for patients and this is reflected by relatively stable plasma levels. The most obvious benefit is convenience of use and better adherence to treatment schedule. Additional advantages may be represented by the opportunity to provide continuous drug delivery in a fashion that could potentially help minimize dyskinesia risk if the drug is used early in the disease course. © 2011 Antonini and Calandrella, publisher and licensee Dove Medical Press Ltd.
Volpato C.,IRCSS San Camillo |
Piccione F.,IRCSS San Camillo |
Silvoni S.,IRCSS San Camillo |
Cavinato M.,IRCSS San Camillo |
And 3 more authors.
Journal of Clinical Neurophysiology | Year: 2010
Aim of this study is to investigate working memory functions in nondemented patients with amyotrophic lateral sclerosis (ALS) using neuropsychological testing and auditory event-related potentials. Twenty-four patients with ALS and 17 age- and education-matched controls underwent a comprehensive neuropsychological assessment, with particular emphasis on working memory functions. Event-related potentials were assessed with an active auditory oddball paradigm. In a subsample (67%) of patients with ALS, the neuropsychological assessment revealed impaired performance on working memory tests (semantic and letter verbal fluency, modified card sorting test, trail making test, digit span, Corsi blocks tapping test, and prose memory). The analysis of event-related potentials showed a significant delay of the N100, P200, and N200 latency in ALS compared with controls. Correlation analysis showed a relation between clinical parameters (disease duration and functional rating scale) and neuropsychological test results (letter fluency and trail making test) and between disease duration and P300 amplitude. The neuropsychological and event-related potentials profile of patients with ALS at an average is consistent with a mild dysfunction of the central executive component of working memory. In conclusion, the results support previously published reports that indicate the involvement of the extramotor functions in a significant subsample of ALS. Copyright © 2010 by the American Clinical Neurophysiology Society.
Soraru G.,University of Padua |
Orsetti V.,University of Padua |
Buratti E.,International Center for Genetic Engineering and Biotechnology |
Baralle F.,International Center for Genetic Engineering and Biotechnology |
And 7 more authors.
Amyotrophic Lateral Sclerosis | Year: 2010
TAR DNA binding protein (TDP-43) is the pathologic substrate of neuronal and glial aggregates in amyotrophic lateral sclerosis (ALS). Pathologic TDP-43 is hyperphosphorylated and cleaved to generate abnormal protein species that accumulate in the cytoplasm. To assess the hypothesis of TDP-43 pathology as a systemic disorder in ALS we analysed the immunohistochemical and biochemical profile of TDP-43 in muscle biopsies of 30 ALS patients and 30 controls. In all ALS muscle biopsies we observed that TDP-43 was constantly present in an intranuclear localization and TDP-43 Western blotting showed only a 43-KDa band as controls. Our results suggest that TDP-43 pathology is probably confined to the central nervous system in ALS.