Abstract：
Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2. Most types of GSDs observed in the cohort were associated with hepatomegaly, which was the most common clinical presentation. This study provides valuable insights into the phenotype and genotype spectrum of GSDs in a cohort of Iranian patients. The identification of novel variants adds to the growing body of knowledge regarding the genetic landscape of GSDs and has implications for genetic counseling and future therapeutic interventions. The diverse nature of GSDs underscores the need for comprehensive genetic testing methods to improve diagnostic accuracy. Continued research in this field will enhance our understanding of GSDs, ultimately leading to improved management and outcomes for individuals affected by these rare metabolic disorders.
摘要：
糖原贮积病(GSD)是一组罕见的遗传性代谢紊乱,基因座,和等位基因异质性。本研究旨在使用全外显子组测序（WES）和变异分析研究来自伊朗的14个家庭的GSD的表型和基因型谱。对14例临床怀疑GSD的患者进行了WES。进行变异分析以鉴定与GSD相关的遗传变异。总共鉴定了13种变体，包括六个新颖的变体，和七个以前报道的基因致病变异，如AGL，G6PC,GAA,PYGL,PYGM,GBE1、SLC37A4和PHKA2。在队列中观察到的大多数类型的GSD与肝肿大有关，这是最常见的临床表现。这项研究为一组伊朗患者中GSD的表型和基因型谱提供了有价值的见解。新变体的鉴定增加了有关GSD遗传景观的知识，并对遗传咨询和未来的治疗干预具有意义。GSD的多样性强调了全面的基因检测方法以提高诊断准确性的必要性。这一领域的持续研究将增进我们对GSDs的理解,最终改善受这些罕见代谢紊乱影响的个体的管理和结局。
