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Targeted exome sequencing in anti-factor H antibody negative HUS reveals multiple variations
R.W. Thergaonkar, A. Narang, B.S. Gurjar, P. Tiwari, M. Puraswani, H. Saini, A. Sinha, B. Varma, , P. HariShow More
Published in Springer Tokyo
PMID: 28939980
Volume: 22
Issue: 3
Pages: 653 - 660
Background: Genetic susceptibility to atypical hemolytic uremic syndrome (aHUS) may lie within genes regulating or activating the alternate complement and related pathways converging on endothelial cell activation. Methods: We tested 32 Indian patients of aHUS negative for antibodies to complement factor H for genetic variations in a panel of 15 genes, i.e., CFH, CFHR1-5, CFI, CFB, C3, CD46, MASP2, DGKE, ADAMTS13, THBD and PLG using next-generation DNA sequencing and for copy number variation in CFHR1-3. Results: Despite absence of a public database of exome variations in the Indian population and limited functional studies, we could establish a genetic diagnosis in 6 (18.8%) patients using a stringent scheme of prioritization. One patient carried a likely pathogenic variation. The number of patients carrying possibly pathogenic variation was as follows: 1 variation: 5 patients, 2 variations: 9 patients, 3 variations: 5 patients, 4 variations: 9 patients, 5 variations: 2 patients and 6 variations: 2 patients. Homozygous deletion of CFHR1-3 was present in five patients; none of these carried a diagnostic genetic variation. Patients with or without diagnostic variation did not differ significantly in terms of enrichment of genetic variations that were rare/novel or predicted deleterious, or for possible environmental triggers. Conclusion: We conclude that genetic testing for multiple genes in patients with aHUS negative for anti-FH antibodies reveals multiple candidate variations that require prioritization. Population data on variation frequency of the Indian population and supportive functional studies are likely to improve diagnostic yield. © 2017, Japanese Society of Nephrology.
About the journal
JournalData powered by TypesetClinical and Experimental Nephrology
PublisherData powered by TypesetSpringer Tokyo