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 journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Article number70
JournalOrphanet Journal of Rare Diseases
Volume7
Issue number1
DOIs
StatePublished - 2012

Fingerprint

Arteriosclerosis
Elastin
Chromatin
Actins
Emphysema
Lung
Lung Diseases
Hyperplasia
Tunica Intima
Mutation
Regulator Genes
Vascular Diseases
Smooth Muscle Myocytes
Blood Vessels
Aorta
Schimke immunoosseous dysplasia
Autopsy
Air
Morbidity
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

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

In: Orphanet Journal of Rare Diseases, Vol. 7, No. 1, 70, 2012.

Research output: Contribution to journalArticle

Morimoto, M, Yu, Z, Stenzel, P, Clewing, JM, Najafian, B, Mayfield, C, Hendson, G, Weinkauf, JG, Gormley, AK, Parham, DM, Ponniah, U, André, JL, Asakura, Y, Basiratnia, M, Bogdanović, R, Bokenkamp, A, Bonneau, D, Buck, A, Charrow, J, Cochat, P, Cordeiro, I, Deschenes, G, Fenkçi, MS, Frange, P, Fründ, S, Fryssira, H, Guillen-Navarro, E, Keller, K, Kirmani, S, Kobelka, C, Lamfers, P, Levtchenko, E, Lewis, DB, Massella, L, McLeod, DR, Milford, DV, Nobili, F, Saraiva, JM, Semerci, CN, Shoemaker, L, Stajić, N, Stein, A, Taha, D, Wand, D, Zonana, J, Lücke, T & Boerkoel, CF 2012, 'Reduced elastogenesis: A clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?', Orphanet Journal of Rare Diseases, vol. 7, no. 1, 70. https://doi.org/10.1186/1750-1172-7-70
Morimoto, Marie ; Yu, Zhongxin ; Stenzel, Peter ; Clewing, J. Marietta ; Najafian, Behzad ; Mayfield, Christy ; Hendson, Glenda ; Weinkauf, Justin G. ; Gormley, Andrew K. ; Parham, David M. ; Ponniah, Umakumaran ; André, Jean Luc ; Asakura, Yumi ; Basiratnia, Mitra ; Bogdanović, Radovan ; Bokenkamp, Arend ; Bonneau, Dominique ; Buck, Anna ; Charrow, Joel ; Cochat, Pierre ; Cordeiro, Isabel ; Deschenes, Georges ; Fenkçi, M. Semin ; Frange, Pierre ; Fründ, Stefan ; Fryssira, Helen ; Guillen-Navarro, Encarna ; Keller, Kory ; Kirmani, Salman ; Kobelka, Christine ; Lamfers, Petra ; Levtchenko, Elena ; Lewis, David B. ; Massella, Laura ; McLeod, D. Ross ; Milford, David V. ; Nobili, François ; Saraiva, Jorge M. ; Semerci, C. Nur ; Shoemaker, Lawrence ; Stajić, Nataša ; Stein, Anja ; Taha, Doris ; Wand, Dorothea ; Zonana, Jonathan ; Lücke, Thomas ; Boerkoel, Cornelius F. / Reduced elastogenesis : A clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?. In: Orphanet Journal of Rare Diseases. 2012 ; Vol. 7, No. 1.
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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, Schimke immuno-osseous dysplasia, SMARCAL1, 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 Bogdanović and Arend Bokenkamp and Dominique Bonneau and Anna Buck and Joel Charrow and Pierre Cochat and Isabel Cordeiro and Georges Deschenes and Fenk{\cc}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{\cc}ois Nobili and Saraiva, {Jorge M.} and Semerci, {C. Nur} and Lawrence Shoemaker and Nataša Stajić and Anja Stein and Doris Taha and Dorothea Wand and Jonathan Zonana and Thomas L{\"u}cke and Boerkoel, {Cornelius F.}",
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T1 - Reduced elastogenesis

T2 - A clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

AU - Morimoto, Marie

AU - Yu, Zhongxin

AU - Stenzel, Peter

AU - Clewing, J. Marietta

AU - Najafian, Behzad

AU - Mayfield, Christy

AU - Hendson, Glenda

AU - Weinkauf, Justin G.

AU - Gormley, Andrew K.

AU - Parham, David M.

AU - Ponniah, Umakumaran

AU - André, Jean Luc

AU - Asakura, Yumi

AU - Basiratnia, Mitra

AU - Bogdanović, Radovan

AU - Bokenkamp, Arend

AU - Bonneau, Dominique

AU - Buck, Anna

AU - Charrow, Joel

AU - Cochat, Pierre

AU - Cordeiro, Isabel

AU - Deschenes, Georges

AU - Fenkçi, M. Semin

AU - Frange, Pierre

AU - Fründ, Stefan

AU - Fryssira, Helen

AU - Guillen-Navarro, Encarna

AU - Keller, Kory

AU - Kirmani, Salman

AU - Kobelka, Christine

AU - Lamfers, Petra

AU - Levtchenko, Elena

AU - Lewis, David B.

AU - Massella, Laura

AU - McLeod, D. Ross

AU - Milford, David V.

AU - Nobili, François

AU - Saraiva, Jorge M.

AU - Semerci, C. Nur

AU - Shoemaker, Lawrence

AU - Stajić, Nataša

AU - Stein, Anja

AU - Taha, Doris

AU - Wand, Dorothea

AU - Zonana, Jonathan

AU - Lücke, Thomas

AU - Boerkoel, Cornelius F.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Elastin

KW - Pulmonary emphysema

KW - Schimke immuno-osseous dysplasia

KW - SMARCAL1

KW - Vascular disease

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U2 - 10.1186/1750-1172-7-70

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