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

MAYORGA, LÍA; ROQUÉ, MARÍA; GAMBONI, BEATRIZ; MAMPEL, ALEJANDRA

MOLECULAR GENETICS AND METABOLISM

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018 vol. 123 p. 331 - 336

1096-7192

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.