Research Centre for Medical Genetics
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RCMG Employees Described the Unique Molecular Genetic Mechanism of IVB Type Mucopolysaccharidosis Pathogenesis

Mucopolysaccharidosis of type IVB (IVB MPS or Morquio B syndrome) is a rare hereditary disease from the group of lysosomal accumulation diseases. MPS IVB is a relatively mild form of GLB1-associated diseases and is characterized mainly by skeletal tissue damage (multiple dysostosis) due to the accumulation of keratan sulfate.

The employees of the laboratories of hereditary metabolic diseases and functional genomics at RCMG characterized a unique molecular genetic mechanism of pathogenesis of MPS IVB. The analysis of the whole genome sequencing of a patient revealed the implantation of a mobile genetic element from the retrotransposon class deep in the intron of the gene GLB1 - the processed pseudogene. Subsequent analysis of a patient’s mRNA, as well as the results of experiments using the technique of expression of minigenes and antisense molecules, revealed that the induction of the processed pseudogene leads to the disruption of splicing the gene GLB1. It was shown that the motifs of splicing enhancers, which are enriched with the sequence of the processed pseudogene, lead to the activation of the latent exon located next to the integration site.

The results are published in the journal «Genomic Medicine» (Q1, Impact Factor 7.227).

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