Whole exome sequencing reveals several novel variants in congenital disorders of glycosylation and glycogen storage diseases in seven patients from Iran

Abstract

Abstract Background Congenital disorder of glycosylation (CDG) and Glycogen storage diseases (GSDs) are inborn metabolic disorders caused by defects in some metabolic pathways. These disorders are a heterogeneous group of diseases caused by impaired O‐ as well as N‐glycosylation pathways. CDG patients show a broad spectrum of clinical presentations; many GSD types (PGM1‐CDG) have muscle involvement and hypoglycemia. Methods We applied WES for all seven patients presenting GSD and CDG symptoms. Then we analyzed the data using various tools to predict pathogenic variants in genes related to the patients' diseases. Results In the present study, we identified pathogenic variants in Iranian patients suffering from GSD and CDG, which can be helpful for patient management, and family counseling. We detected seven pathogenic variants using whole exome sequencing (WES) in known AGL (c.1998A>G, c.3635T>C, c.3682C>T), PGM1 (c.779G>A), DPM1 (c.742T>C), RFT1 (c.127A>G), and GAA (c.1314C>A) genes. Conclusion The suspected clinical diagnosis of CDG and GSD patients was confirmed by identifying missense and or nonsense mutations in PGM1, DPM1, RFT1, GAA, and AGL genes by WES of all 7 cases. This study helps us understand the scenario of the disorder causes and consider the variants for quick disease diagnosis.

Keywords

• CDG
• GSD
• Iran
• Pathogenic genetic variants
• WES