Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a patient with mild intellectual disability and cranio-facial dysmorphisms |
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| Affiliation: | 1. Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway;2. Department for Adult Habilitation, Akershus University Hospital, Oslo, Norway;1. Medical Genetics Institute, Cedars Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles CA, USA;2. Greenwood Genetic Center, Greenwood SC, USA;3. Thompson Center for Autism and Neurodevelopmental Disorders, Department of Child Health, University of Missouri, Columbia MO, USA;4. Signature Genomics, Spokane WA, USA;1. Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK;2. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK;3. Sheffield Clinical Genetics Service, Sheffield Children’s Hospital, Western Bank, Sheffield S10 2TH, UK;4. Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK;5. Clinical Genetics, Addenbrooke’s Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK;6. North West Thames Regional Genetics Service (Kennedy Galton Centre), North West London Hospitals NHS Trust, Harrow, Middlesex HA1 3UJ, UK;7. Department of Clinical Genetics, Children’s Hospital at Westmead, Westmead, NSW 2145, Australia;8. Genetics of Learning Disability Service, Hunter Genetics, Waratah, NSW 2298, Australia;9. Department of Medical Genetics, Royal North Shore Hospital, St. Leonards, NSW 2298, Australia;10. The Genome Centre, John Vane Science Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK;1. Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Pediatrics, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain;2. CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain;3. IDIS, Santiago de Compostela, Spain;4. Secció d''Errors Congènits del Metabolisme (IBC), Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain;5. IDIBAPS, Barcelona, Spain;1. Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden 01307, Germany;2. Instituts für Radiologische Diagnostik am Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany;1. School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia;2. Women’s and Children’s Health Research Institute, North Adelaide, SA 5006, Australia;3. Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia;4. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia;5. South Australian Clinical Genetics Service, SA Pathology at Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia;6. Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK;7. J.C. Self Research Institute, Greenwood Genetics Centre, Greenwood, SC 29646, USA;8. CHRU de Tours, Service de Génétique, Tours 37000, France;9. Inserm U930, UMR Imagerie et Cerveau, Tours 37000, France;10. Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia;11. Robinson Institute, University of Adelaide, Adelaide, SA 5005, Australia;1. Division of Human Genetics, Department of Pediatrics, Inselspital, University of Bern, Switzerland;2. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway;3. Habilitation Service for Adults, Haukeland University Hospital, Bergen, Norway |
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| Abstract: | 2p15p16.1-deletion syndrome was first described in 2007 based on the clinical presentation of two patients. The syndrome is characterized by intellectual disability, autism spectrum disorders, microcephaly, dysmorphic facial features and a variety of congenital organ defects. The precise genotype–phenotype correlation in 2p15-deletion syndrome is not understood. However, greater insight can be obtained by thorough clinical investigation of patients carrying deletions, especially those of small size. We report a 21-year-old male patient with features overlapping the clinical spectrum of the 2p15p16.1-deletion syndrome, such as intellectual disability, dysmorphic facial features, and congenital defects. He carried a 230 kb de novo deletion (chr2:61500346-61733075 bp, hg19), which affects the genes USP34, SNORA70B and XPO1. While there is a lack of functional data on SNORA70B, the involvement of USP34 and XPO1 in the regulation of fundamental developmental processes is well known. We suggest that haploinsufficiency of one or both of these genes is likely to be responsible for the disease in our patient. |
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| Keywords: | Congenital anomalies Dysmorphic features Intellectual disability 2p15p16.1 Deletion syndrome |
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