title: Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt.
abstract: 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.
  
  
  
  Clinical ascertainment of three similar affected patients followed by whole exome sequencing.
  
  
  
  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.
  
  
  
  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.
authors: 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.
authors: Nataliya
authors: N
authors: Di Donato
authors: Medical Genetics Center, Munich, Germany.
authors: Teresa
authors: T
authors: Neuhann
authors: 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.
authors: Anne-Karin
authors: AK
authors: Kahlert
authors: Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany.
authors: Barbara
authors: B
authors: Klink
authors: Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany.
authors: Karl
authors: K
authors: Hackmann
authors: MVZ Prof. Neuhann, Munich, Germany.
authors: Irmingard
authors: I
authors: Neuhann
authors: Department of Sozialpaediatrisches Zentrum, Klinik fuer Kinder und Jugendmedizin, Universitaetsklinikum Dresden, Dresden, Germany.
authors: Barbora
authors: B
authors: Novotna
authors: Department of Sozialpaediatrisches Zentrum, Klinik fuer Kinder und Jugendmedizin, Universitaetsklinikum Dresden, Dresden, Germany.
authors: Jens
authors: J
authors: Schallner
authors: Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany.
authors: Claudia
authors: C
authors: Krause
authors: 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.
authors: Ian A
authors: IA
authors: Glass
authors: Department of Radiology, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA.
authors: Shawn E
authors: SE
authors: Parnell
authors: Medical Genetics Center, Munich, Germany.
authors: Anna
authors: A
authors: Benet-Pages
authors: Medical Genetics Center, Munich, Germany.
authors: Anke M
authors: AM
authors: Nissen
authors: Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland.
authors: Wolfgang
authors: W
authors: Berger
authors: Cologne Center for Genomics, Cologne, Germany.
authors: Janine
authors: J
authors: Altmüller
authors: Cologne Center for Genomics, Cologne, Germany.
authors: Holger
authors: H
authors: Thiele
authors: Institute of Human Genetics, University of Regensburg, Regensburg, Germany.
authors: Bernhard H F
authors: BH
authors: Weber
authors: Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany.
authors: Evelin
authors: E
authors: Schrock
authors: 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.
authors: William B
authors: WB
authors: Dobyns
authors: Gemeinschaftspraxis für Humangenetik, Dresden, Germany.
authors: Andrea
authors: A
authors: Bier
authors: Carl Gustav Carus Faculty of Medicine, Institute for Clinical Genetics, TU Dresden, Dresden, Germany.
authors: Andreas
authors: A
authors: Rump
mesh_terms: D019588:Aging, Premature / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004392:Dwarfism / Q000235:genetics*; D059472:Exome / Q000235:genetics; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D013577:Syndrome
chemical_list: C571394:EXOSC2 protein, human; D016601:RNA-Binding Proteins; D063326:Exosome Multienzyme Ribonuclease Complex
keywords: Clinical genetics; EXOSC2; RNA processing; exosome component 2 protein; novel Mendelian disease