Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice

Nature Communications
Yun Jin PaiN D Greene

Abstract

Glycine decarboxylase (GLDC) acts in the glycine cleavage system to decarboxylate glycine and transfer a one-carbon unit into folate one-carbon metabolism. GLDC mutations cause a rare recessive disease non-ketotic hyperglycinemia (NKH). Mutations have also been identified in patients with neural tube defects (NTDs); however, the relationship between NKH and NTDs is unclear. We show that reduced expression of Gldc in mice suppresses glycine cleavage system activity and causes two distinct disease phenotypes. Mutant embryos develop partially penetrant NTDs while surviving mice exhibit post-natal features of NKH including glycine accumulation, early lethality and hydrocephalus. In addition to elevated glycine, Gldc disruption also results in abnormal tissue folate profiles, with depletion of one-carbon-carrying folates, as well as growth retardation and reduced cellular proliferation. Formate treatment normalizes the folate profile, restores embryonic growth and prevents NTDs, suggesting that Gldc deficiency causes NTDs through limiting supply of one-carbon units from mitochondrial folate metabolism.

References

Jun 26, 1998·Science·A Fleming, A J Copp
Feb 19, 2000·Neurology·J L Van HoveS L Rutledge
Dec 21, 2002·Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology·A PaupeY Ville
May 7, 2004·The European Journal of Neuroscience·Akiko IchinoheKohji Sato
Nov 24, 2004·Neurology·J E Hoover-FongA Hamosh
Dec 15, 2005·American Journal of Medical Genetics. Part a·Derek A Applegarth, Jennifer R Toone
Jan 13, 2006·Annals of Neurology·Stanley H KormanShigeo Kure
Feb 2, 2006·Human Mutation·Shigeo KureYoichi Matsubara
Aug 23, 2006·Nature Reviews. Neuroscience·Henk J BlomRichard H Finnell
Aug 26, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Louisa P E DunlevyNicholas D E Greene
Dec 8, 2006·Theoretical Biology & Medical Modelling·H Frederik NijhoutCornelia M Ulrich
Apr 18, 2007·Brain : a Journal of Neurology·Louisa P E DunlevyNicholas D E Greene
Jan 13, 2009·Pediatric Neurology·Uluc YisEray Dirik
Jan 24, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Andrew E Czeizel
Feb 12, 2009·Prenatal Diagnosis·Nicholas D E Greene, Andrew J Copp
Feb 27, 2009·The Journal of Nutrition·Yvonne LamersJesse F Gregory
Oct 14, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Katie A BurrenNicholas D E Greene
Jul 22, 2010·Annual Review of Nutrition·Anne S Tibbetts, Dean R Appling
Aug 10, 2010·Pediatric Neurology·Yuka SuzukiMitsumasa Fukuda
Feb 25, 2011·The American Journal of Clinical Nutrition·Anna E BeaudinPatrick J Stover
Oct 18, 2011·Journal of Inherited Metabolic Disease·Julia B HennermannJohan L K Van Hove
Dec 18, 2012·Clinical Chemistry and Laboratory Medicine : CCLM·Simon G LamarreJohn T Brosnan
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jessica MombDean R Appling
Jun 25, 2013·Lancet Neurology·Andrew J CoppNicholas D E Greene
Jul 5, 2013·Nature Reviews. Cancer·Jason W Locasale
Aug 13, 2013·Brain : a Journal of Neurology·Kit-Yi LeungNicholas D E Greene
Jul 18, 2014·Annual Review of Neuroscience·Nicholas D E Greene, Andrew J Copp

❮ Previous
Next ❯

Citations

Jul 20, 2016·Annual Review of Nutrition·Margaret E Brosnan, John T Brosnan
Oct 22, 2016·Birth Defects Research. Part A, Clinical and Molecular Teratology·Rita H ShahKit Sing Au
Sep 20, 2016·Cell Metabolism·Gregory S Ducker, Joshua D Rabinowitz
Sep 26, 2017·American Journal of Medical Genetics. Part a·Kit Sing AuHope Northrup
Aug 22, 2018·Annual Review of Nutrition·Martha S FieldPatrick J Stover
Feb 10, 2019·Journal of Inherited Metabolic Disease·Nicholas V StenceJohan L K Van Hove
Jan 1, 2015·Nature Reviews. Disease Primers·Andrew J CoppGary M Shaw
Mar 26, 2015·American Journal of Physiology. Endocrinology and Metabolism·Shannon E WashburnMargaret E Brosnan
Oct 23, 2019·Disease Models & Mechanisms·Sonia SudiwalaNicholas D E Greene
Oct 19, 2019·Scientific Reports·Natalia I KrupenkoSergey A Krupenko
May 30, 2020·Prenatal Diagnosis·Toluwani E TaiwoRichard H Finnell
Oct 1, 2020·Cerebral Cortex·Angelo Harlan De CrescenzoKonstantinos S Zarbalis
Dec 28, 2018·The Journal of Experimental Medicine·Yuxiang Zheng, Lewis C Cantley
Sep 11, 2019·The American Journal of Clinical Nutrition·Joshua W Miller
Jul 26, 2019·NPJ Genomic Medicine·Catherine SarretSergey A Krupenko
Nov 19, 2019·Frontiers in Genetics·Sergey A Krupenko, David A Horita
Mar 14, 2017·Scientifica·Siti W Mohd-ZinNoraishah M Abdul-Aziz
Apr 21, 2018·Molecular Neurobiology·Belisa ParmeggianiGuilhian Leipnitz
Aug 24, 2018·Journal of Developmental Biology·Diana M Juriloff, Muriel J Harris
Apr 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jimi KimRichard H Finnell
Jun 9, 2018·Epilepsia Open·Seda SalarAristea S Galanopoulou
Mar 23, 2018·The American Journal of Clinical Nutrition·John T BrosnanAnne M Molloy
Mar 28, 2019·Journal of Inherited Metabolic Disease·Simon PopeShamima Rahman
Dec 4, 2019·The Journal of Clinical Investigation·Chloe SantosNicholas DE Greene
Jan 9, 2020·The Journal of Nutrition·Margaret E BrosnanJohn T Brosnan
Nov 14, 2018·Birth Defects Research·Laura AvaglianoRichard H Finnell
Nov 26, 2020·International Journal of Molecular Sciences·Yee-Ling TanEn-Pei Isabel Chiang

❮ Previous
Next ❯

Methods Mentioned

BETA
gene-trap
PCR
gene-trapping
protein assay
ion-exchange chromatography

Software Mentioned

Image J
FireCam

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.