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Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

Marie Morimoto12, Zhongxin Yu3, Peter Stenzel4, J Marietta Clewing5, Behzad Najafian6, Christy Mayfield7, Glenda Hendson8, Justin G Weinkauf9, Andrew K Gormley10, David M Parham3, Umakumaran Ponniah10, Jean-Luc André11, Yumi Asakura12, Mitra Basiratnia13, Radovan Bogdanović14, Arend Bokenkamp15, Dominique Bonneau16, Anna Buck17, Joel Charrow18, Pierre Cochat19, Isabel Cordeiro20, Georges Deschenes21, M Semin Fenkçi22, Pierre Frange23, Stefan Fründ24, Helen Fryssira25, Encarna Guillen-Navarro26, Kory Keller27, Salman Kirmani28, Christine Kobelka29, Petra Lamfers30, Elena Levtchenko31, David B Lewis32, Laura Massella33, D Ross McLeod34, David V Milford35, François Nobili36, Jorge M Saraiva37, C Nur Semerci38, Lawrence Shoemaker39, Nataša Stajić14, Anja Stein40, Doris Taha41, Dorothea Wand42, Jonathan Zonana27, Thomas Lücke43 and Cornelius F Boerkoel12*

Author Affiliations

1 Provincial Medical Genetics Program, Department of Medical Genetics, Children's and Women's Health Centre of BC, 4500 Oak Street, Room C234, Vancouver, BC, V6H 3N1, Canada

2 Rare Disease Foundation, Vancouver, British Columbia, Canada

3 Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America

4 Department of Pathology, Oregon Health and Science University, Portland, Oregon, United States of America

5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America

6 Department of Pathology, University of Washington, Seattle, Washington, United States of America

7 Warren Clinic, Tulsa, Oklahoma, United States of America

8 Department of Anatomic Pathology, University of British Columbia and Children’s and Women’s Health Centre of British Columbia, Vancouver, British Columbia, Canada

9 Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

10 Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America

11 Néphrologie Pédiatrique, Hôpital d’Enfants, Centre Hospitalier Universitaire de Nancy, Vandoeuvre lés Nancy Cedex, France

12 Department of Endocrinology & Metabolism, Kanagawa Children’s Medical Center, Yokohama, Japan

13 Department of Pediatric Nephrology, Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

14 Institute of Mother and Child Healthcare of Serbia, Belgrade, Serbia

15 Department of Pediatric Nephrology, VU University Medical Center, Amsterdam, The Netherlands

16 Département de Génétique, Centre Hospitalier Universitaire d’Angers, Angers, France

17 Medizinische Hochschule Hannover, Kinderklinik, Hannover, Germany

18 Division of Genetics, Birth Defects and Metabolism, Children's Memorial Hospital, Chicago, Illinois, United States of America

19 Centre de Référence des Maladies Rènales Rares, Hospices Civils de Lyon and Université de Lyon, Bron Cedex, France

20 Serviço de Genética, Hospital Santa Maria, Centro Hospitalar Lisoboa Norte, Lisbon, Portugal

21 Département de Pédiatrie, Hôpital Robert Debré, Paris, France

22 Department of Internal Medicine, Division of Endocrinology and Metabolism, Cerrahi Hospital, Denizli, Turkey

23 Pediatric Immunology & Hematology Unit, Necker Hospital, Paris, France

24 Department of General Pediatrics, Pediatric Nephrology, University Children’s Hospital Münster, Münster, Germany

25 Department of Medical Genetics, “Aghia Sophia” Children’s Hospital, Athens University Medical School, Athens, Greece

26 Unidad de Genética Médica, Servicio de Pediatría, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

27 Oregon Institute on Disability & Development, Child Development and Rehabilitation Center, Oregon Health & Science University, Portland, Oregon, United States of America

28 Medical Genetics, Mayo Clinic, Rochester, Minnesota, United States of America

29 Department of Genetics, Kaiser Permanente, San Francisco, California, United States of America

30 Mercy Pediatrics and Adolescent Clinic, Clear Lake, Iowa, United States of America

31 Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium

32 Department of Pediatrics, Immunology Program and Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, United States of America

33 Divison of Nephrology, Bambino Gesù Children’s Hospital and Research Institute, Rome, Italy

34 Department of Medical Genetics, Alberta Children’s Hospital, Calgary, Alberta, Canada

35 Department of Nephrology, Birmingham Children’s Hospital, Birmingham, United Kingdom

36 Service de Pédiatrie, Centre Hospitalier Régional Universitaire Hôpital Saint-Jacques, Besançon Cedex, France

37 Consulta de Genética, Hospital Pediátrico de Coimbra, Coimbra, Portugal

38 Department of Medical Genetics, Pamukkale University Hospital, Denizli, Turkey

39 Division of Nephrology, Department of Pediatrics, Kosair Children’s Hospital, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America

40 Universitätsklinikum Essen, Kinderklinik, Essen, Germany

41 Cape Breton Regional Hospital, Sydney, Nova Scotia, Canada

42 Institut für Humangenetik, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany

43 Department of Neuropediatrics, Children’s Hospital, Ruhr-University Bochum, Bochum, Germany

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Orphanet Journal of Rare Diseases 2012, 7:70  doi:10.1186/1750-1172-7-70

Published: 22 September 2012



Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.


We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients.


Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression.


This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.

Schimke immuno-osseous dysplasia; SMARCAL1; Elastin; Vascular disease; Pulmonary emphysema