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Abstract: SA-PO620

Altered UBASH3A Expression May Be Involved in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Phenotypes of Down Syndrome

Session Information

  • Pediatric Nephrology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Lozic, Mirela, Sveuciliste u Splitu Medicinski fakultet, Split, Croatia
  • Vukojevic, Katarina, Sveuciliste u Splitu Medicinski fakultet, Split, Croatia
Background

Congenital anomalies of the kidney and urinary tract (CAKUT) are considered to be the fourth most common major birth defects in Down syndrome (DS) and are up to 30 times more prevalent than in the general population. Due to the lack of insight into its primary pathogenesis, diagnostic and therapeutic possibilities are limited. The UBASH3A gene could be considered a candidate gene for the development of some DS phenotypes as it is mapped to 21q22.3, which is within the critical region for the development of DS. Previously conducted In silico analysis of a database obtained by whole-exome sequencing of patients with CAKUT uncovered UBASH3A as a novel protein-coding candidate gene. We also demonstrated the expression of UBASH3A in normal developing and adult kidneys. Due to the increased gene dose, established expression pattern, and possible role in renal development, altered UBASH3A expression could be involved in the CAKUT DS phenotypes.

Methods

For the immunofluorescence study of UBASH3A in DS, the tissue of kidneys of premature infants and adults diagnosed with DS and CAKUT, along with healthy controls, were used.

Results

UBASH3A exhibited positive expression patterns in DS but differed in intensity and distribution compared to the control samples. In DS, the signal was clearly visible only at a magnification of 100x, while in controls it was clearly visible at 40x, which indicates a significantly reduced intensity. However, in DS we could observe a granular, scattered signal within the nucleus in contrast to the control nuclei, which mostly contained a single punctate signal. This could indicate a large number of abnormal gene products and/or apoptotic processes.

Conclusion

Because of its expression pattern and its mapping to 21q22.3, UBASH3A could be involved in the CAKUT phenotypes of Down syndrome.

Funding

  • Government Support – Non-U.S.