caa a22 4500 445861797 CHVBK 20180317145445.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s00439-011-0947-3 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0947-3 Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia [Elektronische Daten] [Su Kim, Tadeusz Bieganski, Young Sohn, Kazimierz Kozlowski, Mikhail Semënov, Nobuhiko Okamoto, Chi Kim, Ah-Ra Ko, Geung Ahn, Yoon-La Choi, Sung Park, Chang-Seok Ki, Ok-Hwa Kim, Gen Nishimura, Sheila Unger, Andrea Superti-Furga, Dong-Kyu Jin] Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as "leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the SOST gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of SOST. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in SOST. Unlike the other SOST-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism. Springer-Verlag, 2011 Kim Su Center for Pediatric Oncology, National Cancer Center, Goyang, Korea aut Bieganski Tadeusz Department of Diagnostic Imaging, Polish Mother's Memorial Hospital-Reaserch Institute, Lodz, Poland aut Sohn Young Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut Kozlowski Kazimierz Department of Medical Imaging, New Children's Hospital, Sydney, Australia aut Semënov Mikhail Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA, USA aut Okamoto Nobuhiko Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan aut Kim Chi Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Korea aut Ko Ah-Ra Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Korea aut Ahn Geung Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut Choi Yoon-La Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut Park Sung Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut Ki Chang-Seok Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut Kim Ok-Hwa Department of Radiology, Ajou University Hospital, Suwon, Korea aut Nishimura Gen Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Tokyo, Japan aut Unger Sheila Institute of Human Genetics, University of Freiburg Hospital, Freiburg, Germany aut Superti-Furga Andrea Department of Pediatrics, University of Freiburg Hospital, Freiburg, Germany aut Jin Dong-Kyu Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut Human Genetics Springer-Verlag 129/5(2011-05-01), 497-502 0340-6717 129:5<497 2011 129 439 https://doi.org/10.1007/s00439-011-0947-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0947-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kim Su Center for Pediatric Oncology, National Cancer Center, Goyang, Korea aut NATIONALLICENCE 700 1- Bieganski Tadeusz Department of Diagnostic Imaging, Polish Mother's Memorial Hospital-Reaserch Institute, Lodz, Poland aut NATIONALLICENCE 700 1- Sohn Young Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut NATIONALLICENCE 700 1- Kozlowski Kazimierz Department of Medical Imaging, New Children's Hospital, Sydney, Australia aut NATIONALLICENCE 700 1- Semënov Mikhail Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA, USA aut NATIONALLICENCE 700 1- Okamoto Nobuhiko Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan aut NATIONALLICENCE 700 1- Kim Chi Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Korea aut NATIONALLICENCE 700 1- Ko Ah-Ra Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Korea aut NATIONALLICENCE 700 1- Ahn Geung Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Choi Yoon-La Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Park Sung Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut NATIONALLICENCE 700 1- Ki Chang-Seok Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Ok-Hwa Department of Radiology, Ajou University Hospital, Suwon, Korea aut NATIONALLICENCE 700 1- Nishimura Gen Department of Radiology, Tokyo Metropolitan Kiyose Children's Hospital, Tokyo, Japan aut NATIONALLICENCE 700 1- Unger Sheila Institute of Human Genetics, University of Freiburg Hospital, Freiburg, Germany aut NATIONALLICENCE 700 1- Superti-Furga Andrea Department of Pediatrics, University of Freiburg Hospital, Freiburg, Germany aut NATIONALLICENCE 700 1- Jin Dong-Kyu Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, 135-710, Seoul, Gangnam-gu, Korea aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/5(2011-05-01), 497-502 0340-6717 129:5<497 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer