Nataliya Di Donato1, Teresa Neuhann2, Anne-Karin Kahlert3, Barbara Klink4, Karl Hackmann4, Irmingard Neuhann5, Barbora Novotna6, Jens Schallner6, Claudia Krause4, Ian A Glass7, Shawn E Parnell8, Anna Benet-Pages2, Anke M Nissen2, Wolfgang Berger9, Janine Altmüller10, Holger Thiele10, Bernhard H F Weber11, Evelin Schrock4, William B Dobyns12, Andrea Bier13, Andreas Rump4. 1. Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA. 2. Medical Genetics Center, Munich, Germany. 3. Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital of Schleswig-Holstein, Kiel, Germany. 4. Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany. 5. MVZ Prof. Neuhann, Munich, Germany. 6. Department of Sozialpaediatrisches Zentrum, Klinik fuer Kinder und Jugendmedizin, Universitaetsklinikum Dresden, Dresden, Germany. 7. Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA Division of Genetic Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA. 8. Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA. 9. Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland. 10. Cologne Center for Genomics, Cologne, Germany. 11. Institute of Human Genetics, University of Regensburg, Regensburg, Germany. 12. Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA Division of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA Departments of Pediatrics and Neurology, University of Washington, Seattle, Washington, USA. 13. Gemeinschaftspraxis für Humangenetik, Dresden, Germany.
Abstract
BACKGROUND: Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene. METHODS: Clinical ascertainment of three similar affected patients followed by whole exome sequencing. RESULTS: Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8. CONCLUSION: We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
BACKGROUND:Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene. METHODS: Clinical ascertainment of three similar affected patients followed by whole exome sequencing. RESULTS: Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8. CONCLUSION: We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Anne Slavotinek; Doriana Misceo; Stephanie Htun; Linda Mathisen; Eirik Frengen; Michelle Foreman; Jennifer E Hurtig; Liz Enyenihi; Maria C Sterrett; Sara W Leung; Dina Schneidman-Duhovny; Juvianee Estrada-Veras; Jacque L Duncan; Charlotte A Haaxma; Erik-Jan Kamsteeg; Vivian Xia; Daniah Beleford; Yue Si; Ganka Douglas; Hans Einar Treidene; Ambro van Hoof; Milo B Fasken; Anita H Corbett Journal: Hum Mol Genet Date: 2020-08-03 Impact factor: 6.150
Authors: Milo B Fasken; Jillian S Losh; Sara W Leung; Sergine Brutus; Brittany Avin; Jillian C Vaught; Jennifer Potter-Birriel; Taylor Craig; Graeme L Conn; Katherine Mills-Lujan; Anita H Corbett; Ambro van Hoof Journal: Genetics Date: 2016-10-24 Impact factor: 4.562