SCREENING SLC2A1 GENE FOR SEQUENCE AND COPY NUMBER VARIATIONS ASSOCIATED WITH GLUT-1 DEFICIENCY SYNDROME
SCREENING SLC2A1 GENE FOR SEQUENCE AND COPY NUMBER VARIATIONS ASSOCIATED WITH GLUT-1 DEFICIENCY SYNDROME
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Tarih
2020-01-01
Yazarlar
Ornek Erguzeloglu, Cemre
Kara, Bulent
Karacan, Ilker
Ozdemir, Ozkan
Kesim, Yesim
Bebek, Nerses
Ozbek, Ugur
Ugur Iseri, Sibel Aylin
Süreli Yayın başlığı
Süreli Yayın ISSN
Cilt Başlığı
Yayınevi
ISTANBUL UNIV, FAC MEDICINE, PUBL OFF
Dergi Adı
JOURNAL OF ISTANBUL FACULTY OF MEDICINE-ISTANBUL TIP FAKULTESI DERGISI
Özet
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 Polymor- phism (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 al-leles and resulted in GLUT1-DS through haplo insufficiency. Disscussion : 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 fa- cilitated diagnosis in 3 patients.
Açıklama
Anahtar kelimeler
Glucose transporter-1 deficiency syndrome (GLUT1-DS), SLC2A1, de novo variations, CNV analysis, SNP array