Copy number variations in Saudi family with intellectual disability and epilepsy.

Muhammad I Naseer,Gauthaman Kalamegam,Syed Kashif Zaidi,Mohammad H Al-Qahtani,Mahmood Rasool,Adeel G Chaudhary,Mourad Assidi,Shakeel A Ansari,Mohammed M Jan,Farid Ahmed,Fai T Ashgan

doi:10.1186/s12864-016-3091-6

Abstract

BackgroundEpilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Novel Copy number variations (CNVs) are considered as important reason for the numerous neurodevelopmental disorders along with intellectual disability and epilepsy. DNA array based studies contribute to explain a more severe clinical presentation of the disease but interoperation of many detected CNVs are still challenging.ResultsIn order to study novel CNVs with epilepsy related genes in Saudi family with six affected and two normal individuals with several forms of epileptic seizures, intellectual disability (ID), and minor dysmorphism, we performed the high density whole genome Agilent sure print G3 Hmn CGH 2x 400 K array-CGH chips analysis. Our results showed de novo deletions, duplications and deletion plus duplication on differential chromosomal regions in the affected individuals that were not shown in the normal fathe and normal kids by using Agilent CytoGenomics 3.0.6.6 softwear. Copy number gain were observed in the chromosome 1, 16 and 22 with LCE3C, HPR, GSTT2, GSTTP2, DDT and DDTL genes respectively whereas the deletions observed in the chromosomal regions 8p23-p21 (4303127–4337759) and the potential gene in this region is CSMD1 (OMIM: 612279). Moreover, the array CGH results deletions and duplication were also validated by using primer design of deleted regions utilizing the flanked SNPs using simple PCR and also by using quantitative real time PCR.ConclusionsWe found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy. Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome. The advanced high through put array-CGH technique used in this study aim to collect the data base and to identify new mechanisms describing epileptic disorder, may help to improve the clinical management of individual cases in decreasing the burden of epilepsy in Saudi Arabia.

Highlights

Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups
We found some of the de novo deletions and duplication in our study in Saudi family with intellectual disability and epilepsy
Our results suggest that array-CGH should be used as a first line of genetic test for epilepsy except there is a strong indication for a monogenic syndrome

Summary

Introduction

Epilepsy is genetically complex but common brain disorder of the world affecting millions of people with almost of all age groups. Infections, metabolic disorders, brain tumors, head trauma, or stroke are the main reasons of symptomatic epilepsy whereas genetic contributions are the main cause of the idiopathic seizure [2]. In human genetics structural changes are largely unexplored area that may be the common factor of epileptic disease [3]. These changes include deletions, duplications insertions, inversions, and translocations of DNA sequences, and includes copy number differences known as CNVs [4, 5]. CNVs are developing as an important genetic contribution to identify a wide range of epilepsies, such as common new discoveries in epilepsies from genetic generalized epilepsies to the individually rare particular epileptic of encephalopathies [8]. A days various free databases for pathogenic and normal genome variations are available on internet and these are exceptionally valuable tools for interpretation of CNVs identified in normal and patients such as Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources: DECIPHER and Database of Genomic Variants: DGV;)

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