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Background <p>The ALG1-congenital disorder of glycosylation condition is a rare autosomal recessive disorder with approximately 80 patients reported worldwide up to now. This disorder is caused by a deficiency of β1,4 mannosyltransferase due to the pathogenic variants within the <i>ALG1</i> gene which leads to impaired protein glycosylation. This disorder usually causes multiorgan damage. This is the first report of ALG1-CDG cases from Iran who are bearing a novel variant in a homozygote state.</p> Case presentation <p>The clinical and molecular features of three cases have been described. All three cases in this study had experienced seizures at a young age and had developmental delays. They were suffering from speech and learning disabilities, and in one case, cerebral atrophy was also present. Although they all had walking problems, the youngest case gained the ability to walk by occupational therapy. Additionally, they all survived to childhood and adulthood which indicates a mild phenotype. Despite several years of delayed diagnosis, a novel variant p.Leu375Gln was identified in the cases in homozygous form through whole exome sequencing, which ultimately established a diagnosis. The pathogenic effect of the novel variant was assessed computationally. It has been evaluated using prediction tools including SIFT, Poly-Phen2, and Mutation taster. The protein homology modeling was performed, and the variant effect on hydrogen bonds and protein stability was assessed.</p> Conclusion <p>The findings of this study expand our knowledge of clinical and genetic features of ALG1-CDG and present the significant role of next-generation sequencing technologies in the diagnosis of rare disorders.</p>

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ALG1-congenital disorder of glycosylation: report of clinical and genetic features of three new cases and review of literature

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月22日

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  • Faeze Khaghani,
  • Nafiseh Pourbadakhshan,
  • Ehsan Ghayoor Karimiani,
  • Farah Ashrafzadeh,
  • Peyman Eshraghi

摘要

Background

The ALG1-congenital disorder of glycosylation condition is a rare autosomal recessive disorder with approximately 80 patients reported worldwide up to now. This disorder is caused by a deficiency of β1,4 mannosyltransferase due to the pathogenic variants within the ALG1 gene which leads to impaired protein glycosylation. This disorder usually causes multiorgan damage. This is the first report of ALG1-CDG cases from Iran who are bearing a novel variant in a homozygote state.

Case presentation

The clinical and molecular features of three cases have been described. All three cases in this study had experienced seizures at a young age and had developmental delays. They were suffering from speech and learning disabilities, and in one case, cerebral atrophy was also present. Although they all had walking problems, the youngest case gained the ability to walk by occupational therapy. Additionally, they all survived to childhood and adulthood which indicates a mild phenotype. Despite several years of delayed diagnosis, a novel variant p.Leu375Gln was identified in the cases in homozygous form through whole exome sequencing, which ultimately established a diagnosis. The pathogenic effect of the novel variant was assessed computationally. It has been evaluated using prediction tools including SIFT, Poly-Phen2, and Mutation taster. The protein homology modeling was performed, and the variant effect on hydrogen bonds and protein stability was assessed.

Conclusion

The findings of this study expand our knowledge of clinical and genetic features of ALG1-CDG and present the significant role of next-generation sequencing technologies in the diagnosis of rare disorders.