A frame-shift deletion in the PURA gene associates with a new clinical finding: Hypoglycorrhachia. Is GLUT1 a new PURA target?

• Published in: Molecular genetics and metabolism Vol. 123; no. 3; pp. 331 - 336
• Main Authors: Mayorga, Lía, Gamboni, Beatriz, Mampel, Alejandra, Roqué, María
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2018
• Subjects: Blood-Brain Barrier - metabolism; Carbohydrate Metabolism, Inborn Errors - cerebrospinal fluid; Carbohydrate Metabolism, Inborn Errors - genetics; Carbohydrate Metabolism, Inborn Errors - pathology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Down-Regulation; Female; Frameshift Mutation; Glucose - cerebrospinal fluid; Glucose Transporter Type 1 - metabolism; GLUT1; Humans; Hypoglycorrhachia; Infant, Newborn; Leukocytes - metabolism; Monosaccharide Transport Proteins - cerebrospinal fluid; Monosaccharide Transport Proteins - deficiency; Monosaccharide Transport Proteins - genetics; PURA; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional regulator; Whole Exome Sequencing; PURA; GLUT1; Transcriptional regulator; Hypoglycorrhachia
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2017.12.436

PURA is a DNA/RNA-binding protein known to have an important role as a transcriptional and translational regulator. Mutations in the PURA gene have been documented to cause mainly a neurologic phenotype including hypotonia, epilepsy, development delay and respiratory alterations. We report here a patient with a frame-shift deletion in the PURA gene that apart from the classical PURA deficiency phenotype had marked hypoglycorrhachia, overlapping the clinical findings with a GLUT1 deficiency syndrome. SLC2A1 (GLUT1) mutations were discarded, so we hypothesized that GLUT1 could be downregulated in this PURA deficient scenario. We confirmed reduced GLUT1 expression in the patient's peripheral blood cells compared to controls predicting that this could also be happening in the blood-brain barrier and in this way explain the hypoglycorrhachia. Based on PURA's known functions as a transcriptional and translational regulator, we propose GLUT1 as a new PURA target. Further in vitro and in vivo studies are needed to confirm this and to uncover the underlying molecular mechanisms. •A PURA syndrome patient presents with a GLUT1 deficiency-like phenotype.•A reduced expression of GLUT1 is confirmed in the patient's blood cells.•The expression of GLUT1 is proposed to be regulated by PURA.