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

Gormley, Ponniah Umakumaran, Asakura Yumi, Bogdanoviä‡ Radovan, Dominique Bonneau, Charrow Joel, Cordeiro Isabel, Boerkoel, Morimoto Marie, Yu Zhongxin, Stenzel Peter, Clewing J, Najafian Behzad, Mayfield Christy, Hendson Glenda, Weinkauf, Parham, André Jean-Luc, Basiratnia Mitra, Bokenkamp Arend, Buck Anna, Cochat Pierre, Deschenes Georges, Fenkçi M, Frange Pierre, Fründ Stefan, Fryssira Helen, Guillen-Navarro Encarna, Keller Kory, Kirmani Salman, Kobelka Christine, Lamfers Petra, Levtchenko Elena, Lewis, Massella Laura, Mcleod D, Milford, Nobili François, Saraiva, Semerci C, Shoemaker Lawrence, Stajiä‡ Nataša, Stein Anja, Taha Doris, Wand Dorothea, Zonana Jonathan, Lücke Thomas

Description

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 .

Sujets

• SMARCAL1
• Elastin
• Vascular disease
• Emphysema

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 13
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

Morimotoet al. Orphanet Journal of Rare Diseases2012,7:70 http://www.ojrd.com/content/7/1/70

R E S E A R C HOpen Access Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immunoosseous dysplasia? 1,2 3 45 6 7 Marie Morimoto, Zhongxin Yu , Peter Stenzel , J Marietta Clewing , Behzad Najafian , Christy Mayfield , 8 910 310 Glenda Hendson , Justin G Weinkauf , Andrew K Gormley, David M Parham , Umakumaran Ponniah, 11 1213 1415 JeanLuc André, Yumi Asakura, Mitra Basiratnia, Radovan Bogdanović,, Arend Bokenkamp 16 1718 1920 21 Dominique Bonneau, Anna Buck, Joel Charrow, Pierre Cochat, Isabel Cordeiro, Georges Deschenes, 22 2324 2526 27 M Semin Fenkçi, Pierre Frange, Stefan Fründ, Helen Fryssira, Encarna GuillenNavarro, Kory Keller, 28 2930 3132 33 Salman Kirmani, Christine Kobelka, Petra Lamfers, Elena Levtchenko, David B Lewis, Laura Massella, 34 3536 3738 39 D Ross McLeod, David V Milford, François Nobili, Jorge M Saraiva, C Nur Semerci, Lawrence Shoemaker, 14 4041 4227 43 Nataša Stajić, Anja Stein, Dorothea Wand, Doris Taha, Thomas Lücke, Jonathan Zonana 1,2* and Cornelius F Boerkoel

Abstract Background:Arteriosclerosis and emphysema develop in individuals with Schimke immunoosseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations inSMARCAL1(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 withSMARCAL1mutations. 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:Schimke immunoosseous dysplasia,SMARCAL1, Elastin, Vascular disease, Pulmonary emphysema

* Correspondence: [e-mail] 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 Full list of author information is available at the end of the article

© 2012 Morimoto et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.