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. 2018 Nov 20;19(1):200.
doi: 10.1186/s12881-018-0714-6.

Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome

Annes Siji  1 , K N Karthik  1 , Varsha Chhotusing Pardeshi  1 , P S Hari  1 , Anil Vasudevan  2   3
Affiliations

Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome

Annes Siji et al. BMC Med Genet. .

Abstract

Background: Steroid resistant nephrotic syndrome (SRNS) is a genetically heterogeneous disease with significant phenotypic variability. More than 53 podocyte-expressed genes are implicated in SRNS which complicates the routine use of genetic screening in the clinic. Next generation sequencing technology (NGS) allows rapid screening of multiple genes in large number of patients in a cost-effective manner.

Methods: We developed a targeted panel of 17 genes to determine relative frequency of mutations in south Indian ethnicity and feasibility of using the assay in a clinical setting. Twenty-five children with SRNS and 3 healthy individuals were screened.

Results: In this study, novel variants including 1 pathogenic variant (2 patients) and 3 likely pathogenic variants (3 patients) were identified. In addition, 2 novel variants of unknown significance (VUS) in 2 patients (8% of total patients) were also identified.

Conclusions: The results show that genetic screening in SRNS using NGS is feasible in a clinical setting. However the panel needs to be screened in a larger cohort of children with SRNS in order to assess the utility of the customised targeted panel in Indian children with SRNS. Determining the prevalence of variants in Indian population and improvising the bioinformatics-based filtering strategy for a more accurate differentiation of pathogenic variants from those that are benign among the VUS will help in improving medical and genetic counselling in SRNS.

Keywords: Indian population; NGS; SRNS; Targeted re-sequencing.

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Conflict of interest statement

Ethics approval and consent to participate

The Institutional Ethics Committee, St. John’s Medical College, Bangalore, India, approved the study and all participants were recruited after informed consent. The approval number for the study was 171/ 2012. Parents of the children (under the age of 16) consented to participate in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of next generation sequencing variant filtration and annotation. The variants were filtered based on their coverage (minimum coverage of 20×), variant effect, dbSNP, ExAC, 500 exomes and 1000 Genome Project databases status. The filtered variants were visually examined using Integrative Genomics Viewer (IGV) software (http//www.broadinstitute.org/igv), to further filter out variants with possible strand-bias and variants that fall into homopolymeric region. All the filtered variants were annotated as per the ACMG guidelines
See this image and copyright information in PMC

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