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Turkish Journal of Medical Sciences

Abstract

Background/aim: The aim of this study is to investigate the genotype-phenotype correlation in Sanfilippo type B 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, Matrix metalloproteinases (MMP2, MMP9), TIMP-1, TIMP-2, BALP, Cathepsin K, and TRACP-5b were examined by ELISA method in MPS IIIB patients. At the same time, mutations in the NAGLU gene causing this disease were detected by whole exome sequencing, and their correlation with biochemical parameters was investigated.Results: Based on the enzyme analysis results, MMP-9, TIMP1, TIMP-2, and MMP-2 were significantly high, while Cathepsin-K was low in the the study group. Osteoprotegerin levels were similar between the two groups, while Cathepsin K levels were higher in the control group. In this study, genetic analysis of patients with MPS-IIIB disease was performed. The analysis was performed by sequencing all exons and exon-intron junction regions of the NAGLU gene using a next generation sequencing system. In this way, variations were detected qualitatively with high read depths. As a result of the analyses, only 2 patients had a previously pathogenically defined alteration. In addition, as a result of the impact-assessment analyses, alterations that have a modifying effect on protein structure were also detected.Conclusion: Regarding to genetic analysis results, it is necessary to consider the change classified as benign in the OMIM database as pathogenic because the changes (p.Arg737Gly and p.Trp103Cys) found in patients have somehow altered enzyme activity. A novel NAGLU gene mutation, p. Trp103Cys was detected in one patient. The p.Trp103Cys mutation in the first exon was shown the first time, additionally, SIFT and PolyPhen analyses confirmed this variation as "damaging." Therefore, future functional analyses of the variation can be conducted to carry out a more comprehensive study.

Author ORCID Identifier

SEDA GÖKKURT: 0000-0002-9589-3571

İREM PEKER EYÜBOĞLU: 0000-0003-0764-9841

BANU NUR GÜZEL: 0000-0002-3463-5763

ERCAN MIHÇI: 0000-0001-7257-4618

AYŞE ÖZER: 0009-0004-4677-5079

MUSTAFA AKKİPRİK: 0000-0002-1100-765X

DOI

10.55730/1300-0144.5973

Keywords

Mucopolysaccharidoses, NAGLU, NGS, Osteoporosis

First Page

328

Last Page

336

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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