Identification Of The Rs797045105 In The Serac1 Gene By Whole-Exome Sequencing In A Patient Suspicious Of Megdel Syndrome

Introduction: Whole Exome Sequencing (WES) has been increasingly utilized in genetic determinants of various inherited diseases. Methods: We applied WES for a patient presenting 3-Methylglutaconic Aciduria (MEG), Deafness (D), Encephalopathy (E), and Leigh-like (L) syndrome. Then Sanger sequencing was used for the detected variant validation. Results: We found an insertion, rs797045105 (chr6, 158571484, C>CCATG), in the SERAC1 gene with homozygous genotype in the patient and heterozygous genotype in her unaffected parents. Notably, bioinformatics analysis using mutation taster (prob>0.99) and DDIGin (prob=86.51) predicted this mutation as disease-causing. Also, the variant was not present in our database, including 700 exome files. Conclusion: These findings emphasize the pathogenicity of rs797045105 for MEGDEL syndrome. On the other hand, our data shed light on the significance of WES application as a genetic test to identify and characterize the comprehensive spectrum of genetic variation and classification for patients with neuro-metabolic disorders.HighlightsWES is an applicable tool to evaluate genetically metabolic diseases.rs797045105 highly potentially causes MEGDLE syndrome.rs797045105 makes a frameshift change in SERAC1 gene.Plain Language SummaryThe genetic architecture of metabolic traits and diseases is complex. Many genes have role in the pathogenicity of these diseases. Advanced technologies including Whole Exome Sequencing (WES) which can assess many genes simultaneously could be an effective option to find out the mutations causing heterogeneous metabolic disorders. In this study we applied WES for a patient presenting MEGDLE syndrome: a neuro-metabolic disease. After data analysis we found rs797045105 as a disease causing genetic variant for the patient. This pathogenic variation should be considered in genetic profiling of patients with MEGDLE syndrome especially from Southwest of Iran.