Abstract:

Objective To explore the clinical characteristics and genetic mechanisms of patients with Mucolipidosis Ⅲα/β caused by GNPTAB gene mutations. Methods A retrospective analysis was conducted on the clinical data and genetic tests of a confirmed case of Mucolipidosis Ⅲα/β. Various protein prediction tools were used to generate protein models of the wild type and mutant GNPTAB proteins， and computational biology tools were employed to elucidate the differences in protein structure and function between the wild type and mutant variants. Results The patient in this case mainly presented with joint deformities and short stature. Genetic sequencing revealed compound heterozygous mutations in the GNPTAB gene， c.2715 + 1G > A and c.1582T > C； the missense mutation c.1582T > C has not been reported in the literature. By constructing and analyzing three-dimensional models of the mutants， it was found that the c.2715 + 1G > A mutation alters the overall structure of the protein， leading to the loss of protein function， while the c.1582T > C mutation affects the interaction between the subunit of N-acetylglucosamine-1-phosphate transferase and its ligand. Conclusions This case of MLⅢα/β results from a mutation in the GNPTAB gene， including a missense mutation c.1582T > C that has not been previously reported， which expands the spectrum of pathogenic mutations of this gene. Through computational analysis of the protein variants resulting from the GNPTAB gene mutation， the understanding of their structure-function relationship has been elaborated， revealing the molecular mechanisms behind the onset of ML Ⅲα/β disease.

Key words: mucolipidosis, missense mutation, GNPTAB gene, Computational Biology