-
Tytuł:
-
Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.
-
Autorzy:
-
Alfadhel M; Division of Genetics, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, PO Box 22490, Riyadh, 11426, Saudi Arabia. .
Nashabat M; Division of Genetics, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, PO Box 22490, Riyadh, 11426, Saudi Arabia.
Qahtani HA; Medical Imaging Department, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Alfares A; Department of Pediatrics, College of Medicine, Qassim University, Almulyda, Saudi Arabia.
Mutairi FA; Division of Genetics, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, PO Box 22490, Riyadh, 11426, Saudi Arabia.
Shaalan HA; Medical Imaging Department, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Douglas GV; GeneDx, Gaithersburg, MD, 20877, USA.
Wierenga K; Department of Pediatrics, Section of Genetics, The University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK, USA.
Juusola J; GeneDx, Gaithersburg, MD, 20877, USA.
Alrifai MT; Neurology Division, Department of Pediatrics, King Abdullah International Medical Research Centre, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (NGHA), King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Arold ST; Division of Biological and Environmental Sciences and Engineering (BESE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.
Alkuraya F; Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Ali QA; GeneDx, Gaithersburg, MD, 20877, USA.
-
Źródło:
-
Human genetics [Hum Genet] 2016 Nov; Vol. 135 (11), pp. 1263-1268. Date of Electronic Publication: 2016 Aug 01.
-
Typ publikacji:
-
Case Reports; Journal Article
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Berlin : Springer Verlag
Original Publication: Berlin, New York, Springer-Verlag.
-
MeSH Terms:
-
Base Sequence/*genetics
Glycine Plasma Membrane Transport Proteins/*genetics
Hyperglycinemia, Nonketotic/*genetics
Mutation/*genetics
Amino Acid Oxidoreductases/genetics ; Animals ; Carrier Proteins/genetics ; Exome/genetics ; Female ; Glycine/metabolism ; Homozygote ; Humans ; Hyperglycinemia, Nonketotic/pathology ; Infant ; Mice ; Mice, Knockout ; Multienzyme Complexes/genetics ; Phenotype ; Transferases/genetics
-
References:
-
Neuron. 2003 Nov 13;40(4):785-96. (PMID: 14622582)
Neuropadiatrie. 1979 Aug;10(3):209-25. (PMID: 583064)
Bioinformatics. 2006 Jan 15;22(2):195-201. (PMID: 16301204)
Biofactors. 2013 Jul-Aug;39(4):383-91. (PMID: 23553707)
Neurochem Pathol. 1984-1985 Winter;2(4):233-49. (PMID: 6537469)
Cell Mol Life Sci. 2001 May;58(5-6):760-93. (PMID: 11437237)
Amino Acids. 2013 Sep;45(3):463-77. (PMID: 23615880)
Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):229-40. (PMID: 12589194)
Br J Pharmacol. 2015 Dec;172(24):6110-202. (PMID: 26650446)
Biochem Soc Trans. 2006 Feb;34(Pt 1):55-8. (PMID: 16417482)
JPEN J Parenter Enteral Nutr. 1998 Nov-Dec;22(6):393-8. (PMID: 9829614)
Front Mol Neurosci. 2010 Apr 22;3:11. (PMID: 20461146)
FEBS Lett. 2002 Oct 2;529(1):93-101. (PMID: 12354619)
Clin Chim Acta. 1975 Nov 15;65(1):67-74. (PMID: 1238179)
J Biol Chem. 2015 Jan 23;290(4):2150-65. (PMID: 25480793)
Am J Med Genet A. 2006 Jan 15;140(2):186-8. (PMID: 16353254)
Am J Hum Genet. 2015 Sep 3;97(3):457-64. (PMID: 26299366)
Epilepsia. 2012 Dec;53 Suppl 7:3-11. (PMID: 23153204)
Nature. 2015 May 21;521(7552):322-7. (PMID: 25970245)
Behav Brain Res. 1993 Dec 20;58(1-2):175-98. (PMID: 8136044)
-
Substance Nomenclature:
-
0 (Carrier Proteins)
0 (Glycine Plasma Membrane Transport Proteins)
0 (Multienzyme Complexes)
0 (SLC6A9 protein, human)
0 (glycine cleavage system)
EC 1.4.- (Amino Acid Oxidoreductases)
EC 2.- (Transferases)
TE7660XO1C (Glycine)
-
Entry Date(s):
-
Date Created: 20160803 Date Completed: 20170519 Latest Revision: 20181113
-
Update Code:
-
20240104
-
PubMed Central ID:
-
PMC5052303
-
DOI:
-
10.1007/s00439-016-1719-x
-
PMID:
-
27481395
-
Glycine cleavage system (GCS) catalyzes the degradation of glycine and disruption of its components encoded by GLDC, AMT and GCSH are the only known causes of glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH). In this report, we describe a consanguineous family with one child who presented with NKH, but harbored no pathogenic variants in any of the three genes linked to this condition. Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.3: c.1219 A>G (p.Ser407Gly) that segregates with the disease within the family. This variant replaces the highly conserved S407 in the ion-binding site of this glycine transporter and is predicted to disrupt its function. In murine model, knockout of Slc6a9 is associated with equivalent phenotype of NKH, namely respiratory distress and hypotonia. This is the first demonstration that mutation of the glycine transporter can be associated with NKH in humans.
Competing Interests: The authors declare that they have no competing interests. Funding statement This research received no funding grant from public, commercial or not-for-profit sectors.
