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https://ahro.austin.org.au/austinjspui/handle/1/17287
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DC Field | Value | Language |
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dc.contributor.author | Knaus, Alexej | - |
dc.contributor.author | Pantel, Jean Tori | - |
dc.contributor.author | Pendziwiat, Manuela | - |
dc.contributor.author | Hajjir, Nurulhuda | - |
dc.contributor.author | Zhao, Max | - |
dc.contributor.author | Hsieh, Tzung-Chien | - |
dc.contributor.author | Schubach, Max | - |
dc.contributor.author | Gurovich, Yaron | - |
dc.contributor.author | Fleischer, Nicole | - |
dc.contributor.author | Jäger, Marten | - |
dc.contributor.author | Köhler, Sebastian | - |
dc.contributor.author | Muhle, Hiltrud | - |
dc.contributor.author | Korff, Christian | - |
dc.contributor.author | Møller, Rikke S | - |
dc.contributor.author | Bayat, Allan | - |
dc.contributor.author | Calvas, Patrick | - |
dc.contributor.author | Chassaing, Nicolas | - |
dc.contributor.author | Warren, Hannah | - |
dc.contributor.author | Skinner, Steven | - |
dc.contributor.author | Louie, Raymond | - |
dc.contributor.author | Evers, Christina | - |
dc.contributor.author | Bohn, Marc | - |
dc.contributor.author | Christen, Hans-Jürgen | - |
dc.contributor.author | van den Born, Myrthe | - |
dc.contributor.author | Obersztyn, Ewa | - |
dc.contributor.author | Charzewska, Agnieszka | - |
dc.contributor.author | Endziniene, Milda | - |
dc.contributor.author | Kortüm, Fanny | - |
dc.contributor.author | Brown, Natasha | - |
dc.contributor.author | Robinson, Peter N | - |
dc.contributor.author | Schelhaas, Helenius J | - |
dc.contributor.author | Weber, Yvonne | - |
dc.contributor.author | Helbig, Ingo | - |
dc.contributor.author | Mundlos, Stefan | - |
dc.contributor.author | Horn, Denise | - |
dc.contributor.author | Krawitz, Peter M | - |
dc.date | 2018-01-09 | - |
dc.date.accessioned | 2018-03-22T23:32:15Z | - |
dc.date.available | 2018-03-22T23:32:15Z | - |
dc.date.issued | 2018-01-09 | - |
dc.identifier.citation | Genome medicine 2018; 10(1): 3 | - |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/17287 | - |
dc.description.abstract | Glycosylphosphatidylinositol biosynthesis defects (GPIBDs) cause a group of phenotypically overlapping recessive syndromes with intellectual disability, for which pathogenic mutations have been described in 16 genes of the corresponding molecular pathway. An elevated serum activity of alkaline phosphatase (AP), a GPI-linked enzyme, has been used to assign GPIBDs to the phenotypic series of hyperphosphatasia with mental retardation syndrome (HPMRS) and to distinguish them from another subset of GPIBDs, termed multiple congenital anomalies hypotonia seizures syndrome (MCAHS). However, the increasing number of individuals with a GPIBD shows that hyperphosphatasia is a variable feature that is not ideal for a clinical classification. We studied the discriminatory power of multiple GPI-linked substrates that were assessed by flow cytometry in blood cells and fibroblasts of 39 and 14 individuals with a GPIBD, respectively. On the phenotypic level, we evaluated the frequency of occurrence of clinical symptoms and analyzed the performance of computer-assisted image analysis of the facial gestalt in 91 individuals. We found that certain malformations such as Morbus Hirschsprung and diaphragmatic defects are more likely to be associated with particular gene defects (PIGV, PGAP3, PIGN). However, especially at the severe end of the clinical spectrum of HPMRS, there is a high phenotypic overlap with MCAHS. Elevation of AP has also been documented in some of the individuals with MCAHS, namely those with PIGA mutations. Although the impairment of GPI-linked substrates is supposed to play the key role in the pathophysiology of GPIBDs, we could not observe gene-specific profiles for flow cytometric markers or a correlation between their cell surface levels and the severity of the phenotype. In contrast, it was facial recognition software that achieved the highest accuracy in predicting the disease-causing gene in a GPIBD. Due to the overlapping clinical spectrum of both HPMRS and MCAHS in the majority of affected individuals, the elevation of AP and the reduced surface levels of GPI-linked markers in both groups, a common classification as GPIBDs is recommended. The effectiveness of computer-assisted gestalt analysis for the correct gene inference in a GPIBD and probably beyond is remarkable and illustrates how the information contained in human faces is pivotal in the delineation of genetic entities. | - |
dc.language.iso | eng | - |
dc.subject | Anchor biosynthesis defects | - |
dc.subject | Automated image analysis | - |
dc.subject | GPI | - |
dc.subject | Gene | - |
dc.subject | Prediction | - |
dc.title | Characterization of glycosylphosphatidylinositol biosynthesis defects by clinical features, flow cytometry, and automated image analysis. | - |
dc.type | Journal Article | - |
dc.identifier.journaltitle | Genome medicine | - |
dc.identifier.affiliation | Institut für Medizinische Genetik und Humangenetik, Charité Universitätsmedizin Berlin, 13353, Berlin, Germany | - |
dc.identifier.affiliation | Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany | - |
dc.identifier.affiliation | Berlin-Brandenburg School for Regenerative Therapies, Charité Universitätsmedizin Berlin, 13353, Berlin, Germany | - |
dc.identifier.affiliation | Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127, Bonn, Germany | - |
dc.identifier.affiliation | Department of Neuropediatrics, University Medical Center Schleswig Holstein, 24105, Kiel, Germany | - |
dc.identifier.affiliation | Berlin Institute of Health (BIH), 10178, Berlin, Germany | - |
dc.identifier.affiliation | FDNA Inc., Boston, MA, USA | - |
dc.identifier.affiliation | Unité de Neuropédiatrie, Université de Genève, CH-1211, Genève, Switzerland | - |
dc.identifier.affiliation | Danish Epilepsy Centre, DK-4293, Dianalund, Denmark | - |
dc.identifier.affiliation | Institute for Regional Health Services Research, University of Southern Denmark, DK-5000, Odense, Denmark | - |
dc.identifier.affiliation | Department of Pediatrics, University Hospital of Hvidovre, 2650, Hvicovre, Denmark | - |
dc.identifier.affiliation | Service de Génétique Médicale, Hôpital Purpan, CHU, 31059, Toulouse, France | - |
dc.identifier.affiliation | Greenwood Genetic Center, SC29646, Greenwood, USA | - |
dc.identifier.affiliation | Genetische Poliklinik, Universitätsklinik Heidelberg, 69120, Heidelberg, Germany | - |
dc.identifier.affiliation | St. Bernward Krankenhaus, 31134, Hildesheim, Germany | - |
dc.identifier.affiliation | Kinderkrankenhaus auf der Bult, Hannoversche Kinderheilanstalt, 30173, Hannover, Germany | - |
dc.identifier.affiliation | Department for Clinical Genetics, Erasmus MC, 3000, Rotterdam, Netherlands | - |
dc.identifier.affiliation | Institute of Mother and Child Department of Molecular Genetics, 01-211, Warsaw, Poland | - |
dc.identifier.affiliation | Neurology Department, Lithuanian University of Health Sciences, 50009, Kaunas, Lithuania | - |
dc.identifier.affiliation | Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany | - |
dc.identifier.affiliation | Victorian Clinical Genetics Services, Royal Children's Hospital, MCRI, Parkville, Australia | - |
dc.identifier.affiliation | Department of Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia | - |
dc.identifier.affiliation | The Jackson Laboratory for Genomic Medicine, 06032, Farmington, USA | - |
dc.identifier.affiliation | Departement of Neurology, Academic Center for Epileptology, 5590, Heeze, The Netherlands | - |
dc.identifier.affiliation | Department of Neurology and Epileptology and Hertie Institute for Clinical Brain Research, University Tübingen, 72076, Tübingen, Germany | - |
dc.identifier.affiliation | Pediatric Neurology, Children's Hospital of Philadelphia, 3401, Philadelphia, USA | - |
dc.identifier.doi | 10.1186/s13073-017-0510-5 | - |
dc.identifier.pubmedid | 29310717 | - |
dc.type.austin | Journal Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
Appears in Collections: | Journal articles |
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