Balzano N, Villani G R, Grosso M, Izzo P, Di Natale P
Department of Biochemistry and Medical Biotechnologies, Medical School, University of Naples Federico II, 80131, Naples, Italy.
Hum Mutat. 1998;11(4):333. doi: 10.1002/(SICI)1098-1004(1998)11:4<333::AID-HUMU18>3.0.CO;2-G.
Hunter disease (mucopolysaccharidosis type II or MPS II) is an X-linked recessive disorder caused by the deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS) (E.C.3.1.6.13.) involved in the catabolism of mucopolysaccharides dermatan sulfate and heparan sulfate. A large variety of alterations have been detected at the IDS locus. We report here the identification, in 7 unrelated Italian patients, of IDS gene mutations, four of which are novel and have been confirmed by amplification refractory system (ARMS) or restriction analysis. Our findings include: the missense mutation P86L found in a severe phenotype, the splicing mutation G374G and the nonsense mutation W475X, both associated with mild phenotypes. The four novel mutations were: the missense mutations R88P and R88H, associated with severe phenotypes, concerning a position found to be a mutational "hot-spot" for the IDS gene due to a mutation-prone CpG dinucleotide; mutations T1181 and P266H, both in mild patients. Interestingly, four of our mutations are located on exon III of IDS gene, confirming the high mutation frequency of this exon. After this manuscript was submitted, Rathman et al (Am. J.Hum.Genet.59,1202,1996) reported a total of 101 mutations including one R88H which is one of the novel mutations in this report.
亨特氏病（黏多糖贮积症II型或MPS II）是一种X连锁隐性疾病，由溶酶体酶艾杜糖醛酸-2-硫酸酯酶（IDS）（E.C.3.1.6.13.）缺乏所致，该酶参与硫酸皮肤素和硫酸乙酰肝素等黏多糖的分解代谢。在IDS基因座已检测到多种改变。我们在此报告在7名无亲缘关系的意大利患者中鉴定出IDS基因突变，其中4种为新突变，已通过扩增阻滞突变系统（ARMS）或限制性分析得到证实。我们的研究结果包括：在一名严重表型患者中发现错义突变P86L，剪接突变G374G和无义突变W475X，二者均与轻度表型相关。4种新突变分别为：与严重表型相关的错义突变R88P和R88H，由于存在一个易发生突变的CpG二核苷酸，该位置被发现是IDS基因的一个突变“热点”；在轻度患者中发现的突变T1181和P266H。有趣的是，我们鉴定的4种突变位于IDS基因的外显子III上，证实了该外显子的高突变频率。在本稿件提交后，拉特曼等人（《美国人类遗传学杂志》59卷，1202页，1996年）报告了总共101种突变，其中包括本报告中的一种新突变R88H。
