Identification of two novel variants in GNPTAB underlying mucolipidosis II in a Pakistani family.

Background Mucolipidosis II is a rare inherited metabolic disorder characterized by multiple pathologies including coarse facial features, thickened skin, dysostosis multiplex, and skeletal abnormalities. The disorder results due to variants in GNPTAB leading to reduced activity of the enzyme GlcNAc-1-phosphotransferase (GlcNAc-PT). Methods In the present study, a consanguineous Pakistani family was diagnosed with MLII based on clinical and biochemical examination. Peripheral blood samples were collected and subjected to DNA sequencing of all coding exons along with exon-intron boundaries of GNPTAB. Results Molecular investigation of the family identified two novel variants c.25C > T: p.Gln9* (maternal allele) in exon 1 and c.1160C > T: p.Ala387Val (paternal allele) in exon 10 segregating in compound heterozygous form in the affected individuals. Conclusions The GNPTAB variant c.25C > T variant is highly plausible to undergo nonsense-mediated mRNA decay, while the GNPTAB variant c.1160C > T is located in a highly conserved domain, thus both the variants predict to lead to affect the enzyme activity. Two novel variants have been identified in GNPTAB as the underlying cause of ML-II in a Pakistani family. The study thus expands the available GNPTAB mutation spectrum.