Lehtokari V.-L.,University of Helsinki |
Pelin K.,University of Helsinki |
Herczegfalvi A.,Heim Pal Hospital |
Karcagi V.,NIEH |
And 9 more authors.
Neuromuscular Disorders | Year: 2011
Mutations in the nebulin gene are the main cause of autosomal recessive nemaline myopathy, with clinical presentations ranging from mild to severe disease. We have previously reported a nonspecific distal myopathy caused by homozygous missense mutations in the nebulin gene in six Finnish patients from four different families. Here we describe three non-Finnish patients in two unrelated families with distal nemaline myopathy caused by four different compound heterozygous nebulin mutations, only one of which is a missense mutation. One of the mutations has previously been identified in one family with the severe form of nemaline myopathy. We conclude that nemaline myopathy and distal myopathy caused by nebulin mutations form a clinical and histological continuum. Nemaline myopathy should be considered as a differential diagnosis in patients presenting with an early-onset predominantly distal myopathy. © 2011 Elsevier B.V. Source
Bladen C.L.,Institute of Genetic Medicine |
Rafferty K.,Institute of Genetic Medicine |
Straub V.,Institute of Genetic Medicine |
Monges S.,Hospital Pediatria J. P. Garrahan |
And 59 more authors.
Human Mutation | Year: 2013
Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry. © 2013 WILEY PERIODICALS, INC. Source
Boczonadi V.,Northumbria University |
Muller J.S.,Northumbria University |
Pyle A.,Northumbria University |
Munkley J.,Northumbria University |
And 24 more authors.
Nature Communications | Year: 2014
The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease. © 2014 Macmillan Publishers Limited. Source
Ivanov I.S.,Medical university-Plovdiv |
Azmanov D.N.,University of Western Australia |
Ivanova M.B.,Medical University-Sofia |
Chamova T.,Medical University-Sofia |
And 28 more authors.
Molecular Genetics and Metabolism | Year: 2014
Investigation of 31 of Roma patients with congenital lactic acidosis (CLA) from Bulgaria identified homozygosity for the R446* mutation in the PDHX gene as the most common cause of the disorder in this ethnic group. It accounted for around 60% of patients in the study and over 25% of all CLA cases referred to the National Genetic Laboratory in Bulgaria. The detection of a homozygous patient from Hungary and carriers among population controls from Romania and Slovakia suggests a wide spread of the mutation in the European Roma population.The clinical phenotype of the twenty R446* homozygotes was relatively homogeneous, with lactic acidosis crisis in the first days or months of life as the most common initial presentation (15/20 patients) and delayed psychomotor development and/or seizures in infancy as the leading manifestations in a smaller group (5/20 patients). The subsequent clinical picture was dominated by impaired physical growth and a very consistent pattern of static cerebral palsy-like encephalopathy with spasticity and severe to profound mental retardation seen in over 80% of cases. Most patients had a positive family history.We propose testing for the R446* mutation in PDHX as a rapid first screening in Roma infants with metabolic acidosis. It will facilitate and accelerate diagnosis in a large proportion of cases, allow early rehabilitation to alleviate the chronic clinical course, and prevent further affected births in high-risk families. © 2014. Source
Annesi-Maesano I.,University Pierre and Marie Curie |
Annesi-Maesano I.,French Institute of Health and Medical Research |
Baiz N.,University Pierre and Marie Curie |
Baiz N.,French Institute of Health and Medical Research |
And 5 more authors.
Journal of Toxicology and Environmental Health - Part B: Critical Reviews | Year: 2013
Good indoor air quality in schools is important to provide a safe, healthy, productive, and comfortable environment for students, teachers, and other school staff. However, existing studies demonstrated that various air pollutants are found in classrooms, sometimes at elevated concentrations. Data also indicated that poor air quality may impact children's health, in particular respiratory health, attendance, and academic performance. Nevertheless, it should be noted that there are other adverse health effects that are less documented. Few data exist for teachers and other adults that work in schools. Allergic individuals seem to be at a higher risk for adverse respiratory health consequences. Air quality improvement represents an important measure for prevention of adverse health consequences in children and adults in schools. Copyright © 2013 Taylor and Francis Group, LLC. Source