Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families / 中国当代儿科杂志

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.

Analysis of clinical features, biochemical analysis and gene mutations in one Chinese pedigree with neonatal-onset ornithine transcarbamylase deficiency / 中华儿科杂志

<p><b>OBJECTIVE</b>This study aimed at understanding clinical features, biochemistry and gene mutation in one Chinese pedigree which had a neonatal-onset ornithine transcarbamylase deficiency (OTCD) boy, and exploring the significance of ornithine transcarbamylase analysis in prenatal diagnosis.</p><p><b>METHOD</b>The clinical and biochemical data of one case were analyzed. The amino acids in blood and organic acids in urine were analyzed by mass spectrum technology. The OTC gene mutation was detected using polymerase chain reaction (PCR) and DNA direct sequencing for the case, his parents and the fetus amniocyte and her blood after birth.</p><p><b>RESULT</b>The age of onset was 3 days after birth, he began to have poor reaction, difficulty to feed, high blood ammonia, infection, slight metabolic acidosis, which were consistent with the clinical diagnosis of urea cycle disorders. The boy died at the age of 9 days. Citrulline of blood was detected twice, and were 0.86 µm and 1.06 µm, respectively. The orotic acid was elevated (124 µm/M Creatinine), and urine lactic acid was significantly elevated. The citrulline and orotic acid in his parents and their second baby were normal in DBS and urine. One nonsense mutation in the OTC gene was found at the exon 9 (C. 958 C > T) and his mother was the heterozygote, which caused an arginine to terminate the code at position 320 of the protein (R320X). Two other mutations were also detected at intron 9 (C.1005 + 132 InsT) and intron 5 (C.542 + 134 G > G/A). But the analysis of his father's DNA, the fetus amniocyte and her blood was normal.</p><p><b>CONCLUSION</b>The mutation of C. 958 C > T in OTC gene may occur during neonatal period. This mutation would result in a very severe symptom, even die suddenly several days after birth, if it was a boy. It needs more researches to discuss whether the C.1005 + 132 InsT in intron 9 and C.542 + 134 G > G/A in intron 5 were associated with the neonatal-onset OTCD. The DNA analysis of OTC gene could be utilized for the prenatal diagnosis.</p>