Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine

Journal article


Publication Details

Author(s): Kurolap A, Armbruster A, Hershkovitz T, Hauf K, Mory A, Paperna T, Hannappel E, Tal G, Nijem Y, Sella E, Mahajnah M, Ilivitzki A, Hershkovitz D, Ekhilevitch N, Mandel H, Eulenburg V, Baris HN
Journal: American Journal of Human Genetics
Publication year: 2016
Volume: 99
Journal issue: 5
Pages range: 1172-1180
ISSN: 0002-9297


Abstract

Glycine is a major neurotransmitter that activates inhibitory glycine receptors and is a co-agonist for excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors. Two transporters, GLYT1 and GLYT2, regulate extracellular glycine concentrations within the CNS. Dysregulation of the extracellular glycine has been associated with hyperekplexia and nonketotic hyperglycinemia. Here, we report four individuals from two families who presented at birth with facial dysmorphism, encephalopathy, arthrogryposis, hypotonia progressing to hypertonicity with startle-like clonus, and respiratory failure. Only one individual survived the respiratory failure and was weaned off ventilation but has significant global developmental delay. Mildly elevated cerebrospinal fluid (CSF) glycine and normal serum glycine were observed in two individuals. In both families, we identified truncating mutations in SLC6A9, encoding GLYT1. We demonstrate that pharmacologic or genetic abolishment of GlyT1 activity in mice leads to mildly elevated glycine in the CSF but not in blood. Additionally, previously reported slc6a9-null mice and zebrafish mutants also display phenotypes consistent with the affected individuals we examined. Our data suggest that truncating SLC6A9 mutations lead to a distinct human neurological syndrome hallmarked by mildly elevated CSF glycine and normal serum glycine.


FAU Authors / FAU Editors

Armbruster, Anja
Lehrstuhl für Biochemie und Molekulare Medizin
Eulenburg, Volker PD Dr.
Lehrstuhl für Biochemie und Molekulare Medizin
Hannappel, Ewald Prof. Dr.
Professur für Biochemie und Molekulare Neurowissenschaften
Hauf, Katharina
Lehrstuhl für Biochemie und Molekulare Medizin


External institutions with authors

EMMS Nazareth Hospital
Rambam Health Care Campus
Technion - Israel Institute of Technology


How to cite

APA:
Kurolap, A., Armbruster, A., Hershkovitz, T., Hauf, K., Mory, A., Paperna, T.,... Baris, H.N. (2016). Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine. American Journal of Human Genetics, 99(5), 1172-1180. https://dx.doi.org/10.1016/j.ajhg.2016.09.004

MLA:
Kurolap, Alina, et al. "Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine." American Journal of Human Genetics 99.5 (2016): 1172-1180.

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Last updated on 2019-16-01 at 06:08