<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Byrne, Susan</style></author><author><style face="normal" font="default" size="100%">Jansen, Lara</style></author><author><style face="normal" font="default" size="100%">U-King-Im, Jean-Marie</style></author><author><style face="normal" font="default" size="100%">Siddiqui, Ata</style></author><author><style face="normal" font="default" size="100%">Lidov, Hart G W</style></author><author><style face="normal" font="default" size="100%">Bodi, Istvan</style></author><author><style face="normal" font="default" size="100%">Smith, Luke</style></author><author><style face="normal" font="default" size="100%">Mein, Rachael</style></author><author><style face="normal" font="default" size="100%">Cullup, Thomas</style></author><author><style face="normal" font="default" size="100%">Dionisi-Vici, Carlo</style></author><author><style face="normal" font="default" size="100%">Al-Gazali, Lihadh</style></author><author><style face="normal" font="default" size="100%">Al-Owain, Mohammed</style></author><author><style face="normal" font="default" size="100%">Bruwer, Zandre</style></author><author><style face="normal" font="default" size="100%">Al Thihli, Khalid</style></author><author><style face="normal" font="default" size="100%">El-Garhy, Rana</style></author><author><style face="normal" font="default" size="100%">Flanigan, Kevin M</style></author><author><style face="normal" font="default" size="100%">Manickam, Kandamurugu</style></author><author><style face="normal" font="default" size="100%">Zmuda, Erik</style></author><author><style face="normal" font="default" size="100%">Banks, Wesley</style></author><author><style face="normal" font="default" size="100%">Gershoni-Baruch, Ruth</style></author><author><style face="normal" font="default" size="100%">Mandel, Hanna</style></author><author><style face="normal" font="default" size="100%">Dagan, Efrat</style></author><author><style face="normal" font="default" size="100%">Raas-Rothschild, Annick</style></author><author><style face="normal" font="default" size="100%">Barash, Hila</style></author><author><style face="normal" font="default" size="100%">Filloux, Francis</style></author><author><style face="normal" font="default" size="100%">Creel, Donnell</style></author><author><style face="normal" font="default" size="100%">Harris, Michael</style></author><author><style face="normal" font="default" size="100%">Hamosh, Ada</style></author><author><style face="normal" font="default" size="100%">Kölker, Stefan</style></author><author><style face="normal" font="default" size="100%">Ebrahimi-Fakhari, Darius</style></author><author><style face="normal" font="default" size="100%">Hoffmann, Georg F</style></author><author><style face="normal" font="default" size="100%">Manchester, David</style></author><author><style face="normal" font="default" size="100%">Boyer, Philip J</style></author><author><style face="normal" font="default" size="100%">Manzur, Adnan Y</style></author><author><style face="normal" font="default" size="100%">Lourenco, Charles Marques</style></author><author><style face="normal" font="default" size="100%">Pilz, Daniela T</style></author><author><style face="normal" font="default" size="100%">Kamath, Arveen</style></author><author><style face="normal" font="default" size="100%">Prabhakar, Prab</style></author><author><style face="normal" font="default" size="100%">Rao, Vamshi K</style></author><author><style face="normal" font="default" size="100%">Rogers, R Curtis</style></author><author><style face="normal" font="default" size="100%">Ryan, Monique M</style></author><author><style face="normal" font="default" size="100%">Brown, Natasha J</style></author><author><style face="normal" font="default" size="100%">McLean, Catriona A</style></author><author><style face="normal" font="default" size="100%">Said, Edith</style></author><author><style face="normal" font="default" size="100%">Schara, Ulrike</style></author><author><style face="normal" font="default" size="100%">Stein, Anja</style></author><author><style face="normal" font="default" size="100%">Sewry, Caroline</style></author><author><style face="normal" font="default" size="100%">Travan, Laura</style></author><author><style face="normal" font="default" size="100%">Wijburg, Frits A</style></author><author><style face="normal" font="default" size="100%">Zenker, Martin</style></author><author><style face="normal" font="default" size="100%">Mohammed, Shehla</style></author><author><style face="normal" font="default" size="100%">Fanto, Manolis</style></author><author><style face="normal" font="default" size="100%">Gautel, Mathias</style></author><author><style face="normal" font="default" size="100%">Jungbluth, Heinz</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.</style></title><secondary-title><style face="normal" font="default" size="100%">Brain</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Brain</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Agenesis of Corpus Callosum</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Autophagy</style></keyword><keyword><style  face="normal" font="default" size="100%">Cataract</style></keyword><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Cross-Sectional Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Drosophila melanogaster</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Hippocampus</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurodevelopmental Disorders</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Retrospective Studies</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Mar</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">139</style></volume><pages><style face="normal" font="default" size="100%">765-81</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0-49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">Pt 3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/26917586?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Fabretto, Antonella</style></author><author><style face="normal" font="default" size="100%">Kutsche, Kerstin</style></author><author><style face="normal" font="default" size="100%">Harmsen, May-Britt</style></author><author><style face="normal" font="default" size="100%">Demarini, Sergio</style></author><author><style face="normal" font="default" size="100%">Gasparini, Paolo</style></author><author><style face="normal" font="default" size="100%">Fertz, Maria Cristina</style></author><author><style face="normal" font="default" size="100%">Zenker, Martin</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I.</style></title><secondary-title><style face="normal" font="default" size="100%">Eur J Med Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Eur J Med Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Child, Preschool</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, ras</style></keyword><keyword><style  face="normal" font="default" size="100%">Germ-Line Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Heterozygote</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant, Newborn</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Noonan Syndrome</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">SOS1 Protein</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2010</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2010 Sep-Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">53</style></volume><pages><style face="normal" font="default" size="100%">322-4</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Noonan syndrome (NS) is an autosomal dominant, inherited disorder characterized by facial dysmorphism, congenital heart defects, and reduced postnatal growth. Dysregulated RAS-MAPK signalling is the common molecular basis for NS, a genetically heterogeneous disease. Germline mutations in genes encoding small GTPases of the RAS family (KRAS and NRAS), modulators of RAS function (PTPN11, SOS1 and SHOC2) or downstream signal transducers (RAF1) are causative for NS. SOS1 is the second major gene for NS after PTPN11. Compared to patients with mutations in other genes, SOS1 mutation-positive individuals in general tend to have a more favorable outcome, with less short stature and cognitive impairment. We describe two unrelated patients with NS carrying the same heterozygous SOS1 missense mutation (c.1867T &gt; A/p.F623I). The phenotype of both patients is remarkable as they show uncommon clinical features such as pulmonary lymphangiectasis, congenital pleural effusions, severe feeding problems, and laryngomalacia. These findings may be related to the specific mutation present in our two patients, or be part of the SOS1 phenotype. Detailed clinical assessment of large cohorts of patients with NS and SOS1 mutation is required to clarify this initial observation.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/20673819?dopt=Abstract</style></custom1></record></records></xml>