Article Text

other Versions

PDF
Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation
  1. Leah I Elizondo (leahe{at}bcm.tmc.edu)
  1. Baylor College of Medicine, United States
    1. Kyoung Sang Cho (choks69{at}hotmail.com)
    1. Konkuk University, Korea, Republic of
      1. Wei Zhang (wzhang2{at}bcm.tmc.edu)
      1. Baylor College of Medicine, United States
        1. Jiong Yan (jiongyan{at}bcm.tmc.edu)
        1. Baylor College of Medicine, United States
          1. Cheng Huang (chuang{at}sibs.ac.cn)
          1. Baylor College of Medicine, United States
            1. Yan Huang (yanhuang22{at}yahoo.com)
            1. Baylor College of Medicine, United States
              1. Kunho Choi (kchoi{at}cmmt.ubc.ca)
              1. University of British Columbia, Canada
                1. Emily A. Sloan (eas4w{at}virginia.edu)
                1. Baylor College of Medicine, United States
                  1. Kimiko Deguchi (kimikod118{at}aol.com)
                  1. Baylor College of Medicine, United States
                    1. Shu Lou (slou{at}bcm.edu)
                    1. Baylor College of Medicine, United States
                      1. Alireza Baradaran-Heravi (abara{at}cmmt.ubc.ca)
                      1. University of British Columbia, Canada
                        1. Hiroshi Takashima (thiroshi{at}m3.kufm.kagoshima-u.ac.jp)
                        1. Kagoshima University School of Medicine, Japan
                          1. Thomas Lücke (luecke.thomas{at}mh-hannover.de)
                          1. Hanover Medical School, Germany
                            1. Florante A. Quiocho (faq{at}bcm.tmc.edu)
                            1. Baylor College of Medicine, United States
                              1. Cornelius F. Boerkoel (boerkoel{at}interchange.ubc.ca)
                              1. University of British Columbia, Canada

                                Abstract

                                Background: Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive pleiotropic disorder caused by mutations in SMARCAL1. SMARCAL1 encodes an enzyme with homology to the SNF2 chromatin remodeling proteins.

                                Methods: To assess the affect of SMARCAL1 mutations associated with SIOD on SMARCAL1 expression and function, we characterized the effects of various mutations on mRNA and protein expression in patient tissues and cell lines, and the ATPase activity, subcellular localization, and chromatin binding of SMARCAL1 missense mutants.

                                Results: The SIOD-associated SMARCAL1 mutations affected SMARCAL1 protein expression, stability, subcellular localization, chromatin binding, and enzymatic activity. Further, expressing SMARCAL1 missense mutants in Drosophila showed that disease severity was inversely proportionate to overall SMARCAL1 activity.

                                Conclusion: Our results show for the first time that SMARCAL1 binds chromatin in vivo and that SIOD arises from impairment of diverse SMARCAL1 functions.

                                Statistics from Altmetric.com

                                Request permissions

                                If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.