Identification of a novel gene responsible for hyperglycinemia

点击翻译按钮获取中文摘要

Transient neonatal hyperglycinemia (TNH) is clinically or biochemically indistinguishable from nonketotic hyperglycinemia at onset. In the case of TNH the elevated plasma and CFS glycine levels are normalized within 2-8 weeks. To elucidate the pathogenesis of TNH and idntification of a novel gene for hyperglycinemia we studied three patients by screening mutations in the genes that encode components of the glycine cleavage system (GCS). The GCS is a mitochondrial multi-enzyme system that consists of four individual components; P-protein, glycine decarboxylase; T-protein, aminomethyltransferase; H-protein, hydrogen carrier protein; L-protein, dihydrolipoamide dehydrogenase. P, T, H, and L-proteins were encoded by GLDC, AMT, GCSH, and GCSL genes, respectively. Several NKH-causing mutations have been identified in GLDC and AMT. No mutations have been identified in GCSH to date. Heterozygous mutations were identified in all of the three patients suggesting that TNH develops in some heterozygous carriers for nonketotic hyperglycinemia. We identified a splicing mutation of GCSH gene for the first time, indicating that GCSH gene is responsible for hyperglycinemia.