Identification and in-silico analysis of a novel disease-causing variant in the GUSB gene for Mucopolysaccharidosis VII presenting as non-immune fetal hydrops

Abstract

BackgroundMucopolysaccharidosis type VII (MPS VII - Sly disease) is a very rare lysosomal storage disorder caused by biallelic variants in the GUSB gene. Materials and methodsWe report here an Asian Indian family with recurrent non-immune fetal hydrops where lysosomal enzyme analysis in the prenatal sample (cultured amniocytes) revealed the diagnosis of MPS VII and molecular genetic testing of the GUSB gene was performed through next generation sequencing (NGS). ResultsA novel homozygous likely pathogenic missense variant (c.893C>T; p.Ala298Val) was detected in the GUSB gene. Further in silico analysis of the variant using mutation prediction software and in silico protein modeling was done, to understand the pathogenicity of the variant and its effect on the protein structure. Discussion and conclusionNGS can be used for mutation analysis of genes with multiple pseudogenes, but subsequent Sanger sequencing-based validation through selective amplification of the concerned exon from the actual gene is essential for confirmation. This is the first mutation report of the GUSB gene from India.