Identification of a novel variant in exon 5 of galactosamine (N-acetyl)-6-sulfatase gene in mucopolysaccharidosis IVA patients in Indonesia

Objective: Mucopolysaccharidosis IVA (MPS IVA), or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of galactosamine (N-acetyl)-6-sulfatase (GALNS) enzyme that leads to the accumulation of keratan sulfate and chondroitin-6-sulfate in the lysosome and eventually in the tissue or organ damaged. This enzyme deficiency occurs because of mutations in the galactosamine (N-acetyl)-6-sulfatase (GALNS) gene located at locus 16q24.3. GALNS comprises 14 exons, has a size of ~43 kb, and encodes 522 amino acids. Currently, 47 of 368 mutations have been detected in exon 5, indicating that this region is a hotspot of mutations. The objective of this study was to analyze the mutations in exon 5 of GALNS in MPS IVA patients in Indonesia. Materials and Methods: Genomic DNA was isolated from fresh blood samples obtained from patients with MPS IVA and normal individuals at Cipto Mangunkusumo Hospital. Exon 5 of GALNS was amplified using a pair of specific primers, and polymerase chain reaction products were sequenced using an automated sequencing technique. Results: We found a novel missense mutation c.503G>T that alters the amino acid at position 168 from glycine to valine (G168V). Three previously reported variations identified in this study are c.510T>C (Y170), c.566 + 5T>C, and IVS5 + 134G>A. Conclusion: This finding provides new data about variants in exon 5 of GALNS. Further, research is needed to identify variations in other exons and to map the mutation profile in MPS IVA patients in Indonesia.