Clinical and Experimental Nephrology

, Volume 22, Issue 3, pp 653–660 | Cite as

Targeted exome sequencing in anti-factor H antibody negative HUS reveals multiple variations

  • R. W. Thergaonkar
  • Ankita Narang
  • Bahadur Singh Gurjar
  • Pradeep Tiwari
  • Mamta Puraswani
  • Himanshi Saini
  • Aditi Sinha
  • Binuja Varma
  • Mitali Mukerji
  • Pankaj Hari
  • Arvind Bagga
Original article



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.


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.


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.


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.


Hemolytic uremic syndrome Next-generation sequencing Multiplex ligation-dependent probe amplification 



The authors wish to acknowledge the contributions of the following colleagues: Savita Saini from the Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi; Arti Yadav, Jyotsna Singh, and Debasis Dash from the CSIR-Institute of Genomics and Integrative Biology, New Delhi.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest.


The study was supported by Centre Franco-Indien pour la Promotion de la Recherche Avancée (CEFIPRA) vide Project Code no. 4703-1.

Human and animal rights

The study was approved by the Institute Ethics Committee vide IEC/NP-162/10.04.2015.

Informed consent

Informed consent was obtained from all participants. Identifying details of the participants have not been included in the manuscript.

Supplementary material

10157_2017_1478_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 kb)
10157_2017_1478_MOESM2_ESM.docx (32 kb)
Supplementary material 2 (DOCX 32 kb)


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Copyright information

© Japanese Society of Nephrology 2017

Authors and Affiliations

  • R. W. Thergaonkar
    • 1
  • Ankita Narang
    • 2
  • Bahadur Singh Gurjar
    • 3
  • Pradeep Tiwari
    • 2
  • Mamta Puraswani
    • 1
  • Himanshi Saini
    • 1
  • Aditi Sinha
    • 1
  • Binuja Varma
    • 2
  • Mitali Mukerji
    • 2
  • Pankaj Hari
    • 1
  • Arvind Bagga
    • 1
  1. 1.Division of Nephrology, Department of PediatricsAll India Institute of Medical SciencesNew DelhiIndia
  2. 2.CSIR-Institute of Genomics and Integrative BiologyNew DelhiIndia
  3. 3.National Institute of ImmunologyNew DelhiIndia

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