SCREENING SLC2A1 GENE FOR SEQUENCE AND COPY NUMBER VARIATIONS ASSOCIATED WITH GLUT-1 DEFICIENCY SYNDROME/ GLUT-1 EKSIKLIGI SENDROMU ILE ILISKILI SLC2A1 GENINDE YER ALAN DIZI VE KOPYA SAYISI VARYASYONLARININ INCELENMESI

Objective: Glucose transporter-1 deficiency syndrome (GLUT1-DS) is defined as a metabolic encephalopathy that is associated with heterozygous and usually de novo pathogenic variations in the SLC2A1 (solute carrier family2 member1) gene. Materials and Methods: In this study, all coding exons and neighboring intronic regions of SLC2A1 were Sanger sequenced in 12 patients with clinically suspected GLUT1-DS. For de novo variations revealed after sequencing and segregation analysis, we also performed genome wide Single Nucleotide Polymorphism (SNP) genotyping to confirm parental relatedness with the proband. In patients without any sequence variations, real-time quantitative real-time polymerase chain reaction (qPCR) was applied to determine the presence of any copy number variations (CNV). Results: Sanger sequencing followed by bioinformatics analysis, segregation in the family and SNP array genotyping revealed two novel and de novo pathogenic variations associated with the GLUT1-DS phenotype in 2 patients. qPCR results were compatible with one copy loss of SLC2A1 gene in another patient. All variations identified herein are likely to have caused null alleles and resulted in GLUT1-DS through haplo insufficiency. Discussion: In this study we used a series of molecular genetic approaches in order to identify all possible variations in SLC2A1 that may be associated with GLUT1-DS. This collective effort facilitated diagnosis in 3 patients. Keywords: Glucose transporter-1 deficiency syndrome (GLUT1-DS), SLC2A1, de novo variations, CNV analysis, SNP array Amac: GLUT1 eksikligi sendromu (GLUT-1ES) bebeklik caginda baslayan metabolic bir ensefalopati olarak tanimlanmistir. Kolaylastirilmis glikoz tasiyicisi olan GLUT1'i kodlayan SLC2A1 genindeki de novo patojenik varyasyonlardan kaynaklanir. Gerec ve Yontem: Bu calisma kapsaminda, GLUT1-ES klinik suphesi olan 12 hastada SLC2A1 geninin tum ekzonlari Sanger dizileme metodu ile taranmistir. De novo varyantlarin anne baba cocuk uclusu acisindan uyumlulugu Tek Nukleotid Polimorfizmi (SNP) genotiplemesi ile yapilmistir. Sanger analizinde herhangi bir degisikligi olmayan hastalarda, gercek zamanli kantitatif PZR (Polimeraz Zincir Reaksiyonu) analizi ile kopya sayisi degisimleri incelenmistir. Bulgular: Sanger dizileme, biyoinformatik analiz, aile segregasyonu ve SNP genotipleme yaklasimlarinin ardarda uygulanmasi ile 2 hastada GLUT1ES fenotipiyle iliskili iki yeni ve de novo patojenik varyasyon tespit edilmistir. Gercek zama