7. Nghiên cứu tính sinh bệnh của gen PLP1 với bệnh pelizaeus-merzbacher gây chậm phát triển tâm thần

Abstract

This study presents a family case of two male siblings, 6- and 9-year-old boys diagnosed with severe intellectual disability, esotropia, and spastic quadriplegia. Whole-genome sequencing identified a hemizygous c.649G>A (p.Gly217Ser) variant in the PLP1 gene, associated with Pelizaeus–Merzbacher disease-an X-linked genetic disorder characterized by severe intellectual disability, motor developmental delay, spastic quadriplegia, and nystagmus. This variant was reported in the ClinVar database as a variant of uncertain significance. To elucidate its pathogenicity, further analyses were performed, including familial segregation studies and bioinformatics simulations of the PLP1 gene product. Additionally, integrative analysis, including in silico bioinformatics simulations, was conducted to establish genotype-phenotype correlations. The findings indicate that the identified variant is pathogenic, confirming its causal relationship with intellectual disability and associated morphological abnormalities. These results provide a critical basis for accurate genetic counseling and informed reproductive risk assessment in future pregnancies.