Comprehensive mutational screening of genes maintaining the glycine concentrations in the central nervous system

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We have screened 120 families with elevated glycine concentration in plasma and/or cerebrospinal fluids. By the previous screening of GLDC and AMT genes, we identified the causative mutations in 70% of affected families. The purpose of this study is to perform the mutational screening of other candidate gene in the rest of the 35 families. As the candidate genes, which-affect the extracellular glycine concentrations we selected five genes, the GCSH, DLD, LPT, GLYT1, and GLYT2 genes. The GLDC, AMT, and DLD genes encode enzymes which involved in the glycine metabolism while GLYT1 and GLYT2 genes encode specific transporters of glycine. In the GCSH gene, we have identified a base change at the splicing acceptor consensus sequence, AT, in intron 4. No GCSH mutation was detected in other cases. The AT was substituted into GT, which is supposed to abolish the splicing function of this intron. The patients was given a diagnosis as having transient hyperglycinemia. The other mutation identified was missense mutation in LPT gene, which resulted in amino acid substitution form arginine to glycine. The arginine residue is highly conserved among the other spices, suggesting the evolutional importance. No other mutation have been detected in this series of the mutational screening. We concluded that hyperglycinemia can be caused by the other genes than GLDC or AMT.