Increased Wnt and Notch signaling: a clue to the renal disease in Schimke immuno-osseous dysplasia?


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Morimoto M., Myung C., Beirnes K., Choi K., Asakura Y., Bokenkamp A., ...More

ORPHANET JOURNAL OF RARE DISEASES, vol.11, 2016 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 11
  • Publication Date: 2016
  • Doi Number: 10.1186/s13023-016-0519-7
  • Journal Name: ORPHANET JOURNAL OF RARE DISEASES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: Schimke immuno-osseous dysplasia, SMARCAL1 protein, Focal segmental glomerulosclerosis, Wnt signaling pathway, Notch signaling pathway
  • Open Archive Collection: AVESIS Open Access Collection
  • Dokuz Eylül University Affiliated: Yes

Abstract

Background: Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily A-like 1 (SMARCAL1) gene. Changes in gene expression underlie the arteriosclerosis and T-cell immunodeficiency of SIOD; therefore, we hypothesized that SMARCAL1 deficiency causes the focal segmental glomerulosclerosis (FSGS) of SIOD by altering renal gene expression. We tested this hypothesis by gene expression analysis of an SIOD patient kidney and verified these findings through immunofluorescent analysis in additional SIOD patients and a genetic interaction analysis in Drosophila.