División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México.
Eur Rev Med Pharmacol Sci. 2022 Jul;26(14):5115-5127. doi: 10.26355/eurrev_202207_29300.
Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is responsible for degrading heparan and dermatan sulfate. The IDS gene is located on chromosome Xq28; pathological variants in this gene mostly consist of missense mutations and small and larger deletions, which produce different phenotypes. However, there is only one record in our population concerning the molecular mechanism of this disease; a genotype-phenotype description is not available.
There were included 24 unrelated male patients; clinical features were recorded at a database, fluorometric IDS enzyme activity testing was done for each individual, followed by Sanger sequencing to identify mutations.
The mutational spectrum was found in 16 out of 24 Mexican patients with MPS II, and its range of phenotypes was described. The most frequent variants were of the missense type. The most affected exons were exon 3 (c.275T>G, c.284_287del, c.325T>C), exon 8 (c.1035G>C, c.550G>A), exon 9 (c.1403G>C, c.1229_1229del), and exon 7 (c.979A>C; this variant has not been previously reported). Exon 5 (c.438C>T, a non-pathogenic variant) was the least frequent. It was also found that the most severely affected patients were those with large deletions (2 out of 24) [rsaIDS: IDSP1 (P164)x0, FMR1, AFF2 (P164)x2] involving genes and pseudogenes. We found 2 patients with a synonymous mutation in exon 4.
Our results confirmed reports in the literature, since the most frequent variants were reported in exons 3 and 8. However, this result varies from one previous report in our population, which mentions large deletions and rearrangements as the most frequent alterations, since complex rearrangements were not found. According to what has been previously found, the most severely affected patients are those in which a whole gene has been deleted.
亨特综合征，又称黏多糖贮积症 II 型（MPS II），是由于溶酶体酶艾杜糖-2-硫酸酯酶（IDS）缺乏引起的，该酶负责降解硫酸乙酰肝素和硫酸皮肤素。IDS 基因位于 Xq28 染色体上；该基因的病理性变异主要包括错义突变和小的和大的缺失，产生不同的表型。然而，在我们的人群中，只有一个关于这种疾病的分子机制的记录；没有基因型-表型的描述。
共纳入 24 名无关的男性患者；在数据库中记录了临床特征，对每个人进行荧光 IDS 酶活性检测，然后进行 Sanger 测序以鉴定突变。
在 24 名墨西哥 MPS II 患者中发现了 16 种突变谱，并描述了其表型范围。最常见的变异是错义型。受影响最严重的外显子是外显子 3（c.275T>G、c.284_287del、c.325T>C）、外显子 8（c.1035G>C、c.550G>A）、外显子 9（c.1403G>C、c.1229_1229del）和外显子 7（c.979A>C；此变异尚未见报道）。外显子 5（c.438C>T，一种非致病性变异）是最不常见的。还发现，受影响最严重的患者是那些带有大片段缺失（24 例中有 2 例）[rsaIDS：IDSP1（P164）x0、FMR1、AFF2（P164）x2]的患者，这些缺失涉及基因和假基因。我们发现 2 例患者在 4 号外显子有同义突变。
我们的结果证实了文献中的报告，因为最常见的变异发生在 3 号和 8 号外显子。然而，这一结果与我们人群中的一项先前报告不同，该报告提到大片段缺失和重排是最常见的改变，因为没有发现复杂的重排。根据之前的发现，受影响最严重的患者是那些整个基因缺失的患者。
