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

MAYORGA L; GAMBONI, BEATRIZ; MAMPEL, ALEJANDRA; ROQUE M

MOLECULAR GENETICS AND METABOLISM

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2017

1096-7192

PURA is a DNA/RNA-binding protein known to have an important role as a transcriptionaland translational regulator. Mutations in the PURA gene have been documented to causemainly a neurologic phenotype including hypotonia, epilepsy, development delay andrespiratory alterations. We report here a patient with a frame-shift deletion in the PURAgene that apart from the classical PURA deficiency phenotype had markedhypoglycorrhachia, overlapping the clinical findings with a GLUT1 deficiency syndrome.SLC2A1 (GLUT1) mutations were discarded, so we hypothesized that GLUT1 could bedownregulated in this PURA deficient scenario. We confirmed reduced GLUT1 expressionin the patient´s peripheral blood cells compared to controls predicting that this could alsobe 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, wepropose GLUT1 as a new PURA target. Further in vitro and in vivo studies are needed toconfirm this and to uncover the underlying molecular mechanisms.