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Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.
Astuti, Dewi; Sabir, Ataf; Fulton, Piers; Zatyka, Malgorzata; Williams, Denise; Hardy, Carol; Milan, Gabriella; Favaretto, Francesca; Yu-Wai-Man, Patrick; Rohayem, Julia; López de Heredia, Miguel; Hershey, Tamara; Tranebjaerg, Lisbeth; Chen, Jian-Hua; Chaussenot, Annabel; Nunes, Virginia; Marshall, Bess; McAfferty, Susan; Tillmann, Vallo; Maffei, Pietro; Paquis-Flucklinger, Veronique; Geberhiwot, Tarekign; Mlynarski, Wojciech; Parkinson, Kay; Picard, Virginie; Bueno, Gema Esteban; Dias, Renuka; Arnold, Amy; Richens, Caitlin; Paisey, Richard; Urano, Fumihiko; Semple, Robert; Sinnott, Richard; Barrett, Timothy G.
Afiliação
  • Astuti D; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
  • Sabir A; West Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Edgbaston, Birmingham, UK.
  • Fulton P; West Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Edgbaston, Birmingham, UK.
  • Zatyka M; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.
  • Williams D; West Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Edgbaston, Birmingham, UK.
  • Hardy C; West Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Edgbaston, Birmingham, UK.
  • Milan G; Department of Medicine (DIMED), University of Padua, Padua, Italy.
  • Favaretto F; Department of Medicine (DIMED), University of Padua, Padua, Italy.
  • Yu-Wai-Man P; Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Rohayem J; Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
  • López de Heredia M; NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.
  • Hershey T; Cambridge Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Tranebjaerg L; Centrum für Reproduktionsmedizin und Andrologie, WHO Kollaborationszentrum, EAA, Ausbildungszentrum, Universitätsklinikum Münster, Münster, Germany.
  • Chen JH; IDIBELL, Hospital Duran i Reynals, 3ª Planta, Gran Via de L'Hospitalet, 199, E-08908- L'Hospitalet de Llobregat, Barcelona, Spain.
  • Chaussenot A; Centro de Investigación en Red de Enfermedades Raras (CIBERER), U-730, Hospital Duran i Reynals, 3ª Planta, Gran Via de L'Hospitalet, 199, E-08908-L'Hospitalet de Llobregat, Barcelona, Spain.
  • Nunes V; Departments of Psychiatry, Neurology and Radiology, Washington University School of Medicine, St. Louis, Missouri.
  • Marshall B; Department of Clinical Genetics, University Hospital/The Kennedy Centre, Glostrup, Denmark.
  • McAfferty S; Institute of Clinical Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
  • Tillmann V; University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Box 289, Addenbrooke's Hospital, Cambridge, UK.
  • Maffei P; School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, Nice, France.
  • Paquis-Flucklinger V; IDIBELL, Hospital Duran i Reynals, 3ª Planta, Gran Via de L'Hospitalet, 199, E-08908- L'Hospitalet de Llobregat, Barcelona, Spain.
  • Geberhiwot T; Centro de Investigación en Red de Enfermedades Raras (CIBERER), U-730, Hospital Duran i Reynals, 3ª Planta, Gran Via de L'Hospitalet, 199, E-08908-L'Hospitalet de Llobregat, Barcelona, Spain.
  • Mlynarski W; Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona.
  • Parkinson K; Department of Pediatrics, Washington University School of Medicine, One Children's Place, St. Louis, Missouri.
  • Picard V; IT Services, University of Glasgow, Glasgow, UK.
  • Bueno GE; Tartu University Children's Hospital, Tartu, Estonia.
  • Dias R; Department of Medicine (DIMED), University of Padua, Padua, Italy.
  • Arnold A; School of Medicine, IRCAN, UMR CNRS 7284/INSERM U1081/UNS, Nice Sophia-Antipolis University, Nice, France.
  • Richens C; Department of Metabolism, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham, UK.
  • Paisey R; Department of Paediatrics, Medical University of Lodz, Lodz, Poland.
  • Urano F; Alström Syndrome Europe, Woodpecker Cottage, Paignton, S. Devon, UK.
  • Semple R; Association syndrome de Wolfram, Residence Gauguin, Grand-Champ, France.
  • Sinnott R; Unidad de Géstion Clínica de Garrucha, Área de Gestión Sanitaria Norte de Almería, Avd. Dra. Parra, Almería, Spain.
  • Barrett TG; Birmingham Women's and Children's Hospital, Birmingham, UK.
Hum Mutat ; 38(7): 764-777, 2017 07.
Article em En | MEDLINE | ID: mdl-28432734
We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Deficiência de Tiamina / Síndrome de Wolfram / Bases de Dados Genéticas / Diabetes Mellitus / Perda Auditiva Neurossensorial / Anemia Megaloblástica Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Hum Mutat Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Deficiência de Tiamina / Síndrome de Wolfram / Bases de Dados Genéticas / Diabetes Mellitus / Perda Auditiva Neurossensorial / Anemia Megaloblástica Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Hum Mutat Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de publicação: Estados Unidos