Trio-Based Exome Sequencing Revealed Novel Mutation Found in GLDC Gene Results in Glycine Encephalopathy

Background and Aims: Glycine encephalopathy is an inherited rare autosomal recessive inborn metabolic disease, causes high levels of glycine accumulation in the body as a result of abnormal activity of the glycine cleavage enzyme. Our aim is to confirm that novel mutations in GLDC, would result in classic glycine encephalopathy.Methods and Results: Present study involves a couple with a passed away newborn that was affected with poor feeding, lack of energy (lethargy), weak muscle tone (hypotonia) and seizures when was alive. The proband are experiencing their next pregnancy and want to know about the genome of their fetus. Performing WES on proband, identified a novel homozygous pathogenic mutation NM_000170: exon4: c.471-1G>T in GLDC gene. Sanger sequencing confirmed homozygosity of the mutation in the proband. Both parents and their fetus are heterozygous for this variant, suggesting it as the pathogen autosomal recessive disease-causing mutation. The karyotype was reported normal and so mother’s pregnancy will be continued.Conclusion: For the first time in this study, it was confirmed that novel homozygous pathogenic mutation NM_000170: exon4: c.471-1G>T in GLDC gene, can cause glycine encephalopathy.