Ittiwut Chupong, Boonbuamas Sukanya, Srichomthong Chalurmpon, Ittiwut Rungnapa, Suphapeetiporn Kanya, Shotelersuk Vorasuk
1 Department of Pediatrics, Faculty of Medicine, Center of Excellence for Medical Genetics, Chulalongkorn University , Bangkok, Thailand .
2 Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society , Bangkok, Thailand .
Genet Test Mol Biomarkers. 2017 Jan;21(1):58-62. doi: 10.1089/gtmb.2016.0221. Epub 2016 Oct 31.
Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare autosomal recessive lysosomal storage disease, is caused by mutations in the N-acetylgalactosamine-4-sulfatase (arylsulfatase B, or ARSB) gene, resulting in a deficiency of ARSB activity. This study aimed to characterize the clinical and molecular features of four unrelated Thai patients with MPS VI. Two were products of consanguineous marriages.
The diagnosis was confirmed by biochemical and genetic tests. We performed mutation analysis by polymerase chain reaction-sequencing on the entire coding region of the ARSB gene. Array-based comparative genomic hybridization (aCGH) analysis combined with direct sequencing was also used to search for a deletion boundary.
The causative mutations were detected in all cases. Of four different mutations identified, three have never been previously described, which included two missense mutations (p.C155Y and p.R388T) and a deletion encompassing exons 2 and 3. Both missense mutations were absent in 110 unaffected ethnic-matched control chromosomes and an in-house database of 180 Thai exomes. The p.C155Y and p.R388T mutations were located in highly conserved residues. A CGH analysis combined with direct sequencing identified the breakpoints of a large 13,788 base pair deletion. It is the largest deletion of ARSB described to date in patients with MPS VI.
This study expanded the known mutational spectrum of ARSB; we identified three novel mutations; two of which are missense mutations and one that represents the largest deletion mutation identified to date in this gene.
黏多糖贮积症 VI 型（MPS VI；马罗-拉米综合征）是一种罕见的常染色体隐性溶酶体贮积病，由 N-乙酰半乳糖胺-4-硫酸酯酶（芳基硫酸酯酶 B，或 ARSB）基因突变引起，导致 ARSB 活性缺乏。本研究旨在描述 4 例无关的泰国 MPS VI 患者的临床和分子特征。其中 2 例为近亲结婚的后代。
通过生化和基因检测确诊。我们对 ARSB 基因的整个编码区进行聚合酶链反应测序以进行突变分析。基于阵列的比较基因组杂交（aCGH）分析结合直接测序也用于寻找缺失边界。
所有病例均检测到致病突变。在鉴定出的 4 种不同突变中，有 3 种此前从未被描述过，其中包括 2 种错义突变（p.C155Y 和 p.R388T）以及一个包含外显子 2 和 3 的缺失。在 110 条未受影响的种族匹配对照染色体和一个包含 180 个泰国外显子的内部数据库中均未发现这两种错义突变。p.C155Y 和 p.R388T 突变位于高度保守的残基中。aCGH 分析结合直接测序确定了一个 13788 碱基对大缺失的断点。这是迄今为止在 MPS VI 患者中描述的最大的 ARSB 缺失。
本研究扩展了已知的 ARSB 突变谱；我们鉴定出 3 种新突变；其中 2 种为错义突变，1 种是该基因迄今为止鉴定出的最大缺失突变。
