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Kidney Week

Abstract: TH-PO712

Whole-Exome Sequencings Reveal Additional Extracellular Matrix Gene Mutations in Atypical Hemolytic Uremic Syndrome

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Chen, I-Ru, China Medical University Hospital, Taichung City, Taiwan
  • Lin, Hsin-Hung, China Medical University Hospital, Taichung City, Taiwan
  • Yang, Chin-An, China Medical University Hospital, Taichung, Taiwan
  • Chang, Jan-Gowth, China Medical University Hospital, Taichung, Taiwan
  • Wang, Gueijane, China Medical University, Taichung, Taiwan
  • Yeh, Hung chieh, China Medical University Hospital, Taichung City, Taiwan
  • Yang, Ruey-Bing, Academia Sinica, Taipei, Taiwan
  • Huang, Chiu-Ching, China Medical University Hospital, Taichung City, Taiwan
Background


Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by uncontrolled activation of the alternative pathway of complement and induces microangiopathic hemolytic anemia, thrombocytopenia, acute kidney failure and extrarenal manifestations. Most of studies revealed aHUS with pathogenic loss-of-function of complement or gain-of-function regulators of complement. Whether patients with aHUS may have additional extracellular matrix gene mutations is not known at present, we did this study to explore this possibility.

Methods

This study used whole-exome sequencing(WES) to screen our six adult patients, five of them responded to anti-C5 therapy while one patient did not receive anti-C5 treatment due to financial issue. After completing the whole-genome sequencing analyses, we used functional protein association network -STRING for correlation evaluation.

Results

The whole-exome sequencing analysis revealed all six patients were with loss-of-function of complement or gain-of-function regulators of complement (table 1). WES revealed a novel heterozygous mutation in AEBP1 in three aHUS patients, a novel heterozygous mutation in SCUBE1 in two aHUS patients, and a novel heterozygous mutation in WNT2B in two aHUS patients. In addition, one patient had both SCUBE1 and AEBP1 mutations. The STRING network revealed these mutation genes participated in extracellular matrix environment molecule pathways.

Conclusion

Our results demonstrate aHUS patients from Taiwan have additional mutations in extracellular matrix genes (e.g. AEBP1, SCUBE1, and WNT2B). The additional extracellular matrix gene mutations may play a role in the disease severity. We will further clarify the functional molecular interactions between alternative complement pathway and extracellular matrix genes.

Table 1
PatientsComplement related gene mutationExtracellular Matrix Genes mutation
Case 1CFH, CFHR1, CFHR3, CFI, C3, THBDAEBP1
Case 2CFH, CFHR1, CFHR3, CFI, C3, THBD, CFBAEBP1
Case 3CFH, CFHR1, CFHR3, CFI, C3, CD46, THBD, CFBAEBP1, SCUBE1
Case 4CFH, CFHR1, CFHR3, CFI, C3, CFBSCUBE1
Case 5CFH, CFHR1, CFHR3, CFI, C3WNT2B
Case 6CFH, CFHR1, CFHR3, CFI, C3, CD46, THBD, CFBWNT2B