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Kidney Week

Abstract: TH-PO711

Yield of Atypical Hemolytic Uremic Syndrome (aHUS) Genetic Susceptibility Panel Testing

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Bhimarao Nagaraj, Chinmayee, Cincinnati Children''s Hospital Medical C, Loveland, Ohio, United States
  • Denton, James, Cincinnati Children''s Hospital Medical C, Loveland, Ohio, United States
  • Dawson, D. Brian, Cincinnati Children''s Hospital Medical C, Loveland, Ohio, United States
Background

Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal failure secondary to thrombotic microangiopathy (TMA). 90% of HUS cases are associated with infection by Shiga toxin-producing E.coli. About 10% of HUS cases are associated with genetic or acquired defects in the regulation of the alternative complement pathway. In about 60% of individuals affected with aHUS, a specific genetic susceptibility variant may be identified. Clinical genetic testing in patients with aHUS not only informs their disease process but also provides therapeutic and prognostic insight for their management.

Methods

The Genetics and Genomics Laboratory at Cincinnati Children’s Hospital has developed an aHUS genetic susceptibility panel which includes 10 aHUS associated genes. We reviewed the orders we received for this panel over the last two years (June 2016- May 2018) to assess the yield of this genetic test. We also assessed the proportion of pathogenic variants identified in each individual gene on this panel.

Results

Over the last two years, we have tested 338 patients suspected with genetic aHUS through our aHUS genetic susceptibility panel. 29.6% of the patients were heterozygous for the CFHR3-CFHR1 deletion, which is similar to its frequency in the general population. The CFHR3-CFHR1 deletion in the heterozygous state does not confer risk of developing aHUS. 8.3% of the patients were homozygous for the CFHR3-CFHR1 deletion, which is associated with increased risk of developing aHUS. 10.1% of the patients had pathogenic or likely pathogenic sequence variants in one or more of the ten genes on the panel. Two of the patients were homozygous for the CFHR3-CFHR1 deletion in addition to pathogenic sequence variants. Three of the patients had pathogenic sequence variants in two different genes. Overall, about 16.9% of the patients with suspected genetic aHUS were found to carry genetic variations that conferred them increased risk of developing aHUS. The proportion of pathogenic variants identified in each individual gene on this panel are C3 (1.6%), CFB (1.6%), CFH (16.13%), CFHR1 (4.8%), CFHR3 (11.3%), CFHR3- CFHR1 homozygous deletion (45.2%), CFHR5 (3.2%), CFI (14.5%), DGKE (3.2%), CD46 (6.5%) and THBD (1.6%).

Conclusion

This study emphasizes the significance of genetic analysis in patients with suspected aHUS.