Comparative small RNA sequencing reveals candidate functional miRNAs in nonketotic hyperglycinemia
Description
Nonketotic hyperglycinemia (NKH) is a rare autosomal recessive (AR) inherited disorder of amino acid metabolism known as glycine encephalopathy. Clinical manifestations arise as a result of enzyme deficiency involved in glycine degradation. Currently, there is no suitable treatment method available to change the prognosis of NKH; existing treatments aim to prevent and eliminate the accumulation of glycine in the body. MicroRNAs (miRNAs) are small non-coding RNAs that function as transcriptional and post-transcriptional regulators of gene expression. The growing significance of miRNAs in cellular mechanisms offers new horizons in deciphering the genotype-phenotype correlations in diseases, and assists in the early diagnosis, prognosis, and treatment options. Although their potential, the miRNAs involvement in NKH is yet to be elucidated. Here we report that comparative profiling of the small RNA sequencing data generated from diagnosed clinical samples. We conducted multi-step bioinformatics analysis to predict, annotate, and characterize candidate miRNAs for their cellular targets, associated pathways, and contribution to the disease mechanism. In our study, nine known miRNAs are identified to be associated with NKH using at least two different tools. Our study is the first to demonstrate altered miRNA profiles in cases where the expression of AMT and GLDC genes is reduced. We further demonstrated the alteration in miRNA levels in cases where the expression of AMT and GLDC genes is reduced. We hope that the candidate miRNAs could serve as a specific and robust biomarker for early diagnosis of NKH.