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