中文摘要：

为了研究粘多糖贮积症Ⅱ型（MPSⅡ）患者发病的分子遗传学机制,以便为今后的产前基因诊断等创造必要的前提条件,文章先采用尿糖胺聚糖（GAGs）定性检测法对疑似MPSⅡ的先证者进行初诊,然后采用PCR、PCR产物直接测序法对先证者及其家系成员进行突变检测。在检出IDS基因c.876del2新突变后,对随机采集的120例正常对照和其他非Ⅱ型MPS患者包括MPSⅠ,Ⅳ,Ⅵ三型的病人共15例的IDS基因exon6进行序列分析,同时采用不同物种突变点序列的保守性分析法,以及直接测定患儿及其家庭相关成员IDS酶活性的方法对该新突变进行致病性分析。结果显示：先证者尿检呈强阳性（GAGs＋＋＋）;其IDS基因exon6编码区内存在c.876-877delTC新缺失突变,为半合子突变,而其母、其姐为杂合突变;正常对照和其他非Ⅱ型MPS患者的IDS基因exon6的检测结果均未发现该突变;不同物种氨基酸序列的同源性比对显示：c.876-877delTC突变所在的位置即p.292-293的苯丙氨酸（F）谷氨酰胺（Q）高度保守;酶活性测定的结果显示：先证者的IDS酶活性仅为2.3nmol/4h/mL,大大低于正常值, 而其父的为641．9nmol／4h／mL，其母的血浆酶活性为95．8nmol／4h／mL，其姐的为103．2nmol／4h／mL。说明所发现的c．876—877delTC缺失移码突变是一种新的病理性突变，是该MPSⅡ患儿发病的根本内因。

英文摘要：

The purpose of this study was to understand the molecular genetic mechanism of mucopolysaccharidosis type Ⅱ （MPS Ⅱ）and to provide a prerequisite for future prenatal gene diagnosis.A preliminary diagnosis was made by qualitative detection of Urinary Glycosaminoglycans of the suspected MPSⅡ proband.Then,mutation detection was performed on the proband and his family members with PCR and direct sequencing of PCR products.After the novel mutation of c.876 del 2 in IDS gene was detected, sequence analysis was performed on exon 6 oflDS gene of the 135 cases, which consisted of 120 randomly selected normal controls, and other 15 patients with MPS Ⅰ, Ⅳ, and Ⅵ other than MPS Ⅱ. Besides, the pathogenicity of the novel mutation was analyzed with the following 2 methods： conservative analysis of the sequence of mutation spots of different species and the direct test of the IDS enzyme activity of the patient and his relative family members. The result of uroscopy of the proband was strong positive （GAGs＋＋＋ ）. There was a novel deletion mutation of c.876-877 del TC in the coding region of exon 6 of IDS gene, which was a hemizygous mutation. However, the mutation of his mother and sister was a heterozygous mutation. Detection of the exon 6 oflDS gene showed that the mutation was not found among normal controls and other patients with MPS Ⅰ, Ⅳ, and Ⅵ other than MPS Ⅱ. Homology comparison of amino acid sequences from different species showed that the phenylalanine （F） glutamine （Q） of the mutation site of c.876-877 del TC located in p.292-293 was highly conserved. The activity of IDS enzyme of the proband was only 2.3 nmol/4 lgmL, which was much lower than normal; but the activity oflDS enzyme of his father, mother and sister was 641.9 nmol/4 h/mL, 95.8 nmol/41gmL and 103.2 nmol/4h/mL, respectively. These results illustrated that the deletion and frame-shift mutation of c.876-877 del TC detected was a novel pathologic mutation, which was the underlying cause of MPS Ⅱ of this patient