Association of certain biochemical parameters related to bone cycle with genotype in MPS IIIB patients.

Background/aim: The aims of this study are to investigate the genotype-phenotype correlation in Sanfilippo type B (MPS IIIB) patients in terms of bone formation/resorption parameters and to determine the release/inhibition of biomarkers accompanying osteoporosis.

Materials and methods: Plasma levels of osteoprotegerin (OPG), matrix metalloproteinases (MMP2 and MMP9), tissue inhibitors of metalloproteinase (TIMP1 and TIMP2) and cathepsin K were examined using the ELISA method for a MPS IIIB patient group and a control group. At the same time, mutations in the NAGLU gene causing the disease were identified by whole exome sequencing, and their correlation with biochemical parameters was investigated.

Results: The enzyme analysis results showed that MMP2, MMP9, TIMP1, and TIMP2 were significantly high in the study group, while cathepsin K was low. OPG levels were similar between the two groups. The genetic analysis of patients with MPS IIIB was performed by sequencing all exons and exon-intron junction regions of the NAGLU gene using a next-generation sequencing (NGS) system. In this way, variations were detected qualitatively with high read depths. The analyses found that only two patients had a previously pathogenically defined alteration. In addition, the impact assessment analyses detected alterations with a modifying effect on protein structure.

Conclusion: The genetic analysis results indicate the need to consider a variation classified as benign in the OMIM database as pathogenic because the variations found in the patients (p.Arg737Gly and p.Trp103Cys) have somehow altered enzyme activity. The mutation p.Trp103Cys, a novel NAGLU gene mutation in the first exon, was detected in one patient; additionally, SIFT and PolyPhen analyses confirmed it as damaging. Further functional analyses of this variation should be conducted to gather more comprehensive information.