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  • 标题:Genotype-phenotype correlation of gangliosidosis mutations using in silico tools and homology modeling
  • 本地全文:下载
  • 作者:Li Ou ; Sarah Kim ; Chester B. Whitley
  • 期刊名称:Molecular Genetics and Metabolism Reports
  • 印刷版ISSN:2214-4269
  • 出版年度:2019
  • 卷号:20
  • 页码:1-9
  • DOI:10.1016/j.ymgmr.2019.100495
  • 出版社:Elsevier B.V.
  • 摘要:Gangliosidoses, including GM1-gangliosidosis and GM2-gangliosidosis (Tay-Sachs disease and Sandhoff disease), are lysosomal disorders resulting from enzyme deficiencies and accumulation of gangliosides. Phenotypes of gangliosidoses range from infantile, late-infantile, juvenile, and to the adult form. The genotype-phenotype correlation is essential for prognosis and clinical care planning for patients with a gangliosidosis condition. Previously, we have developed a method to establish the genotype-phenotype correlation of another lysosomal disease, mucopolysaccharidosis type I, with in silico tools. This same method was applied to analyze the genotype and phenotype of 38 patients diagnosed with a gangliosidosis disease in the United States. Out of 40 mutations identified, 3 were novel, including p.Tyr192His and p.Phe556Ser of the GLB1 gene and p.Gly461Val of the HEXA gene. Furthermore, the mutant protein structure of all missense mutations was constructed by homology modeling. A systemic structural analysis of these models revealed the specific mechanisms of how each mutation may lead to the disease. In summary, the method developed in this study holds promise as a tool that can be broadly applicable to other lysosomal diseases and monogenic diseases.
  • 关键词:Genotype-phenotype correlation ; In silico ; Gangliosidosis ; Disease subtype ; Lysosomal disorder
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