Background and objectives

Mucopolysaccharidosis type VI (MPS VI) is a rare, autosomal recessive lysosomal storage disorder caused by deficient enzymatic activity of N-acetyl galactosamine-4-sulphatase, which is caused by mutations in the arylsulphatase B (ARSB) gene. To date, 163 different types of mutations in the ARSB have been reported. However, the full mutation spectrum in the MPS VI phenotype is still not known. The aim of this study was to perform molecular testing of the ARSB gene in the patient and his family members to confirm MPS VI.

Methods

Molecular characterisation of the ARSB gene was performed using Sanger sequencing. We studied a child suspected of having MPS VI and 16 other relatives.

Results

We identified a C-to-T transition resulting in an exchange of the Arg codon 160 for a premature stop codon (R160*, in exon 2). The transition was in CpG dinucleotides.

Interpretation and conclusions

The study provided some insights into the genotype-phenotype relationship in MPS VI and the importance of genetic testing when diagnosing MPS, which is not a mandatory test for the diagnosis and only very occasionally performed. Additionally, we present here the history of a family with confirmed MPS VI, which is extremely rare especially in south-eastern Poland. What is more, the position where the mutation is located is very interesting because it is the region of CpG, which is the site of the methylation process. Thus, this opens the possibility of a new approach indicating the involvement of an epigenetic mechanism that should be examined in the context of the pathomechanism of MPS.

中文翻译：

---

波兰一个家庭的VI型粘多糖贮积症病例。基因检测和基因型-表型关系在粘多糖贮积症诊断中的重要性

背景和目标

VI型粘多糖贮积症（MPS VI）是一种罕见的常染色体隐性遗传溶酶体贮积症，由芳基硫酸酯酶B（ ARSB）基因突变引起的N-乙酰半乳糖胺4-硫酸酯酶活性不足引起。迄今为止，已经报道了 163 种不同类型的ARSB突变。然而，MPS VI 表型中的完整突变谱仍然未知。本研究的目的是对患者及其家人的ARSB基因进行分子检测，以确认 MPS VI。

方法

使用 Sanger 测序对ARSB基因进行分子表征。我们研究了一名疑似患有 MPS VI 的儿童和其他 16 名亲属。

结果

我们确定了一个 C 到 T 转换，导致 Arg 密码子 160 交换为过早终止密码子（R160 *，在外显子 2 中）。转变是在 CpG 二核苷酸中。

解释和结论

该研究对 MPS VI 中的基因型-表型关系以及诊断 MPS 时基因检测的重要性提供了一些见解，这不是诊断的强制性测试，只是偶尔进行。此外，我们在这里介绍了一个确诊 MPS VI 的家庭的历史，这在波兰东南部尤其罕见。更重要的是，突变所在的位置非常有趣，因为它是CpG的区域，是甲基化过程的位点。因此，这开启了一种新方法的可能性，表明表观遗传机制的参与，应该在 MPS 的病理机制的背景下进行检查。