Mucopolysaccharidoses type VII (Sly syndrome): New uncertain pathogenic variants in GUSB gene

Area of Science:

• Genetics
• Biochemistry
• Developmental Biology

Background:

• Mucopolysaccharidoses (MPS) encompass a group of genetic disorders characterized by glycosaminoglycan (GAG) accumulation.
• Eight distinct MPS subtypes are recognized, stemming from eleven identified enzyme deficiencies.
• MPS VII, or Sly syndrome, arises from GUSB gene defects, leading to beta-glucuronidase enzyme dysfunction.

Purpose of the Study:

• To investigate a case of non-immune hydrops fetalis (NIHF) suspected to be MPS VII.
• To identify the genetic basis of MPS VII in a fetus with pathological findings.

Main Methods:

• Post-mortem examination of a 22-week fetus with NIHF.
• Histological analysis revealing characteristic cellular changes.
• Genetic testing of the GUSB gene.

Main Results:

• The fetus exhibited classical NIHF signs and histiocytes with microvacuolated cytoplasm.
• Genetic analysis identified biallelic variants of uncertain significance in exon 8 of the GUSB gene.
• Histological findings supported a diagnosis of MPS VII, linking the GUSB variants to the disease.

Conclusions:

• The study confirms a case of MPS VII in a fetus presenting with NIHF.
• The identified GUSB gene variants, though of uncertain significance, are implicated in the observed MPS VII phenotype.
• This case highlights the diagnostic utility of integrating clinical, histological, and genetic findings in rare genetic disorders.