Investigation of Inherited Causes of Autosomal Recessive Non-syndromic Epilepsy in an Iranian Family Using Whole Exome Sequencing Method

Document Type : Original Article (s)

Authors

1 PhD Student, Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

2 Assistant Professor, Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

3 Associate Professor, Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

Abstract

Background: The cause of epilepsy in most of cases is unknown but inherited causes can play a role in its incidence. Recently, many researches have been conducted in the field of epilepsy. The aim of this study was to identify gene(s) responsible in an Iranian family with autosomal recessive non-syndromic epilepsy using whole exome sequencing (WES) method.Methods: In this experimental study, genomic DNA was extracted from whole blood belonging to three affected persons and a healthy individual and whole exome sequencing was performed using Illumina Hiseq2000 platform. At first, variants classification were carried out based on mutation types, position of the mutation and their allele frequencies and then, prioritization was performed via two approaches. Sanger sequencing was carried out for RNF216 confirming the variant [NM_207111.3 (RNF216): (g.5780794G > A), (c.854C > T)].Findings: From 130855 variants, 85% were single nucleotide variants and 15% were indels. One third of them located in intergenic and intronic regions, one third located in 3’and 5’ UTRs and one third located in exonic and splice site regions. 3.8% and 3.4% of variants had allele frequencies below 0.01 in ExAC and 1000 genome project databases, respectively. By using the two prioritization approaches, a variant in RNF216 gene [NM_207111.3 (RNF216): (g.5780794G > A), (c.854C > T)] was selected as a prior candidate. However, this variant did not co-segregate with the disease in all of the members of this family.Conclusion: Exome sequencing has been considered as a tool for studying genetic causes of Mendelian disorders; but it has some limitations. Mutation in the non-coding regions of the genome, clinical heterogeneity of disease, wrong clinical diagnosis, phenocopy, and technical and analytical limitations can be considered as a reason that we could not find gene(s) responsible for the disease in this family.

Keywords

References

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Journal of Isfahan Medical School
Volume 34, Issue 407 - Serial Number 407
September and October 2017
Pages 1362-1368

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History

  • Receive Date: 26 July 2016
  • Revise Date: 06 May 2024
  • Accept Date: 06 April 2022

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