No authors have conflicts of interest to report.
Article first published online: 7 AUG 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 9, pages 2204–2213, September 2012
How to Cite
Baradaran-Heravi, A., Raams, A., Lubieniecka, J., Cho, K. S., DeHaai, K. A., Basiratnia, M., Mari, P.-O., Xue, Y., Rauth, M., Olney, A. H., Shago, M., Choi, K., Weksberg, R. A., Nowaczyk, M. J.M., Wang, W., Jaspers, N. G.J. and Boerkoel, C. F. (2012), SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo. Am. J. Med. Genet., 158A: 2204–2213. doi: 10.1002/ajmg.a.35532
Alireza Baradaran-Heravi and Anja Raams contributed equally to the study.
How to Cite this Article: Baradaran-Heravi A, Raams A, Lubieniecka J, Cho KS, DeHaai KA, Basiratnia M, Mari P-O, Xue Y, Rauth M, Olney AH, Shago M, Choi K, Weksberg RA, Nowaczyk MJM, Wang W, Jaspers NGJ, Boerkoel CF. 2012. SMARCAL1 deficiency predisposes to non-Hodgkin lymphoma and hypersensitivity to genotoxic agents in vivo. Am J Med Genet Part A. 158A:2204–2213.
- Issue published online: 24 AUG 2012
- Article first published online: 7 AUG 2012
- Manuscript Accepted: 16 MAY 2012
- Manuscript Received: 7 MAR 2012
- March of Dimes
- Gillson Longenbaugh Foundation
- Dana Foundation
- New Investigator Development Award, Microscopy, and Administrative Cores of the Mental Retardation and Developmental Disabilities Research Center at Baylor College of Medicine
- Burroughs Wellcome Foundation
- National Institute of Diabetes, Digestive, and Kidney Diseases, NIH. Grant Number: R21DK065725
- Association Autour D'Emeric et D'Anthony
- The Little Giants Foundation
- Intramural Research Program of the National Institute on Aging. Grant Number: Z01 AG000657-08
- National Institute of Health (US)
- Schimke immuno-osseous dysplasia;
- non-Hodgkin lymphoma;
- T-cell immunodeficiency;
- genotoxic agents
Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder with prominent skeletal, renal, immunological, and ectodermal abnormalities. It is caused by mutations of SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), which encodes a DNA stress response protein. To determine the relationship of this function to the SIOD phenotype, we profiled the cancer prevalence in SIOD and assessed if defects of nucleotide excision repair (NER) and nonhomologous end joining (NHEJ), respectively, explained the ectodermal and immunological features of SIOD. Finally, we determined if Smarcal1del/del mice had hypersensitivity to irinotecan (CPT-11), etoposide, and hydroxyurea (HU) and whether exposure to these agents induced features of SIOD. Among 71 SIOD patients, three had non-Hodgkin lymphoma (NHL) and one had osteosarcoma. We did not find evidence of defective NER or NHEJ; however, Smarcal1-deficient mice were hypersensitive to several genotoxic agents. Also, CPT-11, etoposide, and HU caused decreased growth and loss of growth plate chondrocytes. These data, which identify an increased prevalence of NHL in SIOD and confirm hypersensitivity to DNA damaging agents in vivo, provide guidance for the management of SIOD patients. © 2012 Wiley Periodicals, Inc.