@article{c3bf795f7d4f43e6b3027f5ae30ccf62,
title = "Reduced elastogenesis: A clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?",
abstract = "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.",
keywords = "Elastin, Pulmonary emphysema, SMARCAL1, Schimke immuno-osseous dysplasia, Vascular disease",
author = "Marie Morimoto and Zhongxin Yu and Peter Stenzel and Clewing, {J. Marietta} and Behzad Najafian and Christy Mayfield and Glenda Hendson and Weinkauf, {Justin G.} and Gormley, {Andrew K.} and Parham, {David M.} and Umakumaran Ponniah and Andr{\'e}, {Jean Luc} and Yumi Asakura and Mitra Basiratnia and Radovan Bogdanovi{\'c} and Arend Bokenkamp and Dominique Bonneau and Anna Buck and Joel Charrow and Pierre Cochat and Isabel Cordeiro and Georges Deschenes and Fenk{\c c}i, {M. Semin} and Pierre Frange and Stefan Fr{\"u}nd and Helen Fryssira and Encarna Guillen-Navarro and Kory Keller and Salman Kirmani and Christine Kobelka and Petra Lamfers and Elena Levtchenko and Lewis, {David B.} and Laura Massella and McLeod, {D. Ross} and Milford, {David V.} and Fran{\c c}ois Nobili and Saraiva, {Jorge M.} and Semerci, {C. Nur} and Lawrence Shoemaker and Nata{\v s}a Staji{\'c} and Anja Stein and Doris Taha and Dorothea Wand and Jonathan Zonana and Thomas L{\"u}cke and Boerkoel, {Cornelius F.}",
note = "Funding Information: We are grateful to all of our patients and family members who have contributed to this study. We thank Theresa Sturby, Barbara A. Antalffy and Pauline Grennan for preparation of tissue. This work was supported in part by grants from the March of Dimes (6-FY02-136 to CF Boerkoel), the Gillson Longenbaugh Foundation (CF Boerkoel), the Dana Foundation (CF Boerkoel) and the New Development Award, Microscopy, and Administrative Cores of the Mental Retardation and Developmental Disabilities Research Center at Baylor College of Medicine (CF Boerkoel), the Burroughs Wellcome Foundation (1003400 to CF Boerkoel), the National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health (R03 DK062174 and R21DK065725 to CF Boerkoel), New Investigator Award from the SickKids Foundation – Canadian Institutes of Health Research: Institute of Human Development, Child and Youth Health (CF Boerkoel), the Michael Smith Foundation for Health Research (CI-SCH-O1899(07–1) to CF Boerkoel), the Association Autour D{\textquoteright}Emeric et D{\textquoteright}Anthony (CF Boerkoel) and The Little Giants Foundation (CF Boerkoel). CF Boerkoel is a scholar of the Michael Smith Foundation for Health Research and a Clinical Investigator of the Child & Family Research Institute.",
year = "2012",
doi = "10.1186/1750-1172-7-70",
language = "English",
volume = "7",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central Ltd.",
number = "1",
}