SCA15 due to large ITPR1 deletions in a cohort of 333 white families with dominant ataxia

BACKGROUND: Deletions in ITPR1, coding for the inositol-triphosphate receptor type 1, have been recently identified in spinocerebellar ataxia type 15 (SCA15). OBJECTIVE: To determine the frequency and the phenotypical spectrum of SCA15. DESIGN: Taqman polymerase chain reaction (258 index cases) or single-nucleotide polymorphism genome-wide genotyping (75 index cases). SETTING: A collaboration between the Centre de Recherche de l'Institut de Cerveau et de la Moelle Epiniere of the Salpetriere Hospital (Paris, France) and the Molecular Genetics Unit of the National Institute of Aging (Bethesda, Maryland). Patients Index cases of 333 families with autosomal dominant cerebellar ataxia negative for CAG repeat expansions in coding exons. MAIN OUTCOME MEASURES: Detection of ITPR1 copy number alterations. RESULTS: A deletion of ITPR1 was found in 6 of 333 families (1.8%), corresponding to 13 patients with SCA15. Age at onset ranged from 18 to 66 years (mean [SD] age, 35 [16] years). The symptom at onset was cerebellar gait ataxia, except in 1 patient with isolated upper limb tremor. Although families were tested irrespective of their phenotype, patients with SCA15 had a homogeneous phenotype and were characterized by a slowly progressive cerebellar ataxia. However, pyramidal signs (2 patients) and mild cognitive problems (2 patients) were occasionally present. Radiologic findings showed global or predominant vermian cerebellar atrophy in all patients. CONCLUSIONS: In this series, ITPR1 deletions were rare and accounted for approximately 1% of all autosomal dominant cerebellar ataxias. The SCA15 phenotype mostly consists of a slowly progressive isolated cerebellar ataxia with variable age at onset; an additional pyramidal syndrome and problems in executive functions may be present

The EURANOS cooperative framework for preparedness and management strategies of the long-term consequences of a radiological event

Experience following the Chernobyl accident in the CIS and the EU has clearly demonstrated that policies and strategies for long-term management of extensive contaminated areas must give due importance to social, cultural, ethical, environmental, economic and political factors beyond the sole radiological protection and health perspective. What is at stake in the long-term response to such a situation is the sustainable rehabilitation of living conditions in affected territories, in a context in which each person can actively contribute to his own protection. Preparing or developing rehabilitation of living conditions in a territory affected by long-lasting radioactive contamination is a broader issue of governance as it must address all affected dimensions and articulate the actions of the various concerned actors at the local, regional and national level. To respond to this challenge, a specific research project was implemented by Mutadis, CEPN, NRPA and AgroParisTech from April 2004 to June 2009 in the framework of the EURANOS integrated programme. The overall objective of this project was “to develop a strategic and methodological framework that can inform or assist national authorities in Europe in establishing arrangements for the long-term management and the sustainable rehabilitation of living conditions in extensive areas that may be contaminated as a result of an accident or malevolent act involving radioactive material”. The proposed framework describes a two-steps method allowing national and local authorities together with key stakeholders to establish arrangements and preparation strategies in the perspective of long-term management of a radiological event. It may also be used to develop rehabilitation strategies in countries affected by long-lasting radioactive contamination. This framework aims to set up favourable conditions for stakeholders (in particular local communities) to engage effectively and sustainably in the cooperative development of post-accident preparation or management strategies. The first step of the method aims to frame the issue and identify conditions for stakeholders to engage in rehabilitation preparedness or management strategies. The second step aims to develop a local-national cooperation platform gathering local and national, private and public actors to develop together preparation or management strategies