There are four distinct forms of Sanfilippo syndrome (MPS type III), each of which is an autosomal lysosomal storage disorder. These forms are caused by abnormalities in one of four lysosomal enzymes. This study aimed to identify possible genetic variants that contribute to Sanfilippo IIIB in 14 independent families in Southwest Iran. Patients were included if their clinical features and enzyme assay results were suggestive. The patients were subsequently subjected to Sanger Sequencing to screen for Sanfilippo-related genes. Additional investigations have been conducted using various computational analyses to determine the probable functional effects of diagnosed variants. Five distinct variations were identified in the gene. This included two novel variants in two distinct families and three previously reported variants in 12 distinct families. All of these variations were recognized as pathogenic using the MutationTaster web server. In silico analysis showed that all detected variants affected protein structural stability; four destabilized protein structures, and the fifth variation had the opposite effect. In this study, two novel variations in the gene were identified. The results of this study positively contribute to the mutation diversity of the gene. To identify new disease biomarkers and therapeutic targets, precision medicine must precisely characterize and account for genetic variations. New harmful gene variants are valuable for updating gene databases concerning Sanfilippo disease variations and NGS gene panels. This may also improve genetic counselling for rapid risk examinations and disease surveillance.

中文翻译：

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IIIB型MPS患者的遗传特征：五种致病基因变异的描述

Sanfilippo 综合征（MPS III 型）有四种不同的形式，每种形式都是常染色体溶酶体贮积症。这些形式是由四种溶酶体酶之一的异常引起的。本研究旨在确定伊朗西南部 14 个独立家族中可能导致 Sanfilippo IIIB 的遗传变异。如果患者的临床特征和酶测定结果具有提示性，则将其纳入其中。随后对患者进行桑格测序，以筛选与桑菲利波相关的基因。使用各种计算分析进行了额外的研究，以确定诊断变异的可能功能影响。该基因中发现了五种不同的变异。这包括两个不同家族中的两个新变异以及 12 个不同家族中先前报道的三个变异。使用 MutationTaster 网络服务器将所有这些变异识别为致病性。计算机分析表明，所有检测到的变异都会影响蛋白质结构的稳定性；四种不稳定的蛋白质结构，第五种变化具有相反的效果。在这项研究中，鉴定出了该基因的两个新变异。这项研究的结果对该基因的突变多样性做出了积极贡献。为了识别新的疾病生物标志物和治疗靶点，精准医学必须精确表征和解释遗传变异。新的有害基因变异对于更新有关 Sanfilippo 疾病变异和 NGS 基因组的基因数据库很有价值。这也可能改善快速风险检查和疾病监测的遗传咨询。