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

Marie Morimoto, Zhongxin Yu, Peter Stenzel, J. Marietta Clewing, Behzad Najafian, Christy Mayfield, Glenda Hendson, Justin G. Weinkauf, Andrew K. Gormley, David M. Parham, Umakumaran Ponniah, Jean Luc André, Yumi Asakura, Mitra Basiratnia, Radovan Bogdanović, Arend Bokenkamp, Dominique Bonneau, Anna Buck, Joel Charrow, Pierre CochatIsabel Cordeiro, Georges Deschenes, M. Semin Fenkçi, Pierre Frange, Stefan Fründ, Helen Fryssira, Encarna Guillen-Navarro, Kory Keller, Salman Kirmani, Christine Kobelka, Petra Lamfers, Elena Levtchenko, David B. Lewis, Laura Massella, D. Ross McLeod, David V. Milford, François Nobili, Jorge M. Saraiva, C. Nur Semerci, Lawrence Shoemaker, Nataša Stajić, Anja Stein, Doris Taha, Dorothea Wand, Jonathan Zonana, Thomas Lücke, Cornelius F. Boerkoel

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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

Original languageEnglish
Article number70
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 2012
Externally publishedYes


  • Elastin
  • Pulmonary emphysema
  • Schimke immuno-osseous dysplasia
  • Vascular disease


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