Ventriculomegaly and hydrocephalus are associated with loss of function of glycine decarboxylase (Gldc) in mice and in humans suffering from Non-Ketotic Hyperglycinemia (NKH), a neurometabolic disorder characterised by accumulation of excess glycine.
Nonketotic hyperglycinemia (NKH) is a neuro-metabolic disorder caused by a deficiency in the glycine cleavage system (GCS) and glycine transporter 1 (GlyT1).
Using CRISPR/Cas9, we knocked out the gldc gene and showed that gldc-/- fish recapitulate GE on a molecular level and present a motor phenotype reminiscent of severe GE symptoms.
The two variants of GLDC gene identified probably underlie the pathogenesis of non-ketotic hyperglycinemia in this family, and also enrich the mutational spectrum of GLDC gene.
Possibly damaging variants were observed in SCZ: A203V, S801N in GLDC, near the atypical nonketotic hyperglycinemia causative mutations (A202V, A802V); G825D in GLDC, a potential neural tube defect causative mutation; and R253X in AMT.
Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans.
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).