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粘多糖贮积症为糖胺聚糖降解代谢障碍所引起的一组遗传代谢病。根据不同的酶缺陷,可分为8型,鉴于我国I型最常见,本文就MPS-I的临床特征、a-L-艾杜糖苷酸酶基因结构、突变类型、特点及检测方法加以综述。 相似文献
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目的 对经酶学确诊的粘多糖贮积症Ⅰ型患者进行α-L-艾杜糖苷酸酶(α-L-iduronidase,IDUA)基因突变检测,了解中国北方地区粘多糖贮积症Ⅰ型轻型患者基因突变特点.方法 应用PCR扩增技术及直接测序技术对11例中国北方地区经酶学确诊的粘多糖贮积症Ⅰ型患者IDUA基因14个外显子及相邻区域进行突变筛查,同时进行亲本来源分析.结果 11例患者中检测出7种基因突变:A79V、R89Q、R89w、E178K、G197S、L346R和W626X.7种突变均为已报道过子,11例中6例患者为纯合改变,1例为无义突变杂合子;发现了9种已知多态性位点.结论 中国北方地区粘多糖贮积症Ⅰ型轻型患者IDUA基因的突变特点可能不同于其他国家和地区.Abstract: Objective Mucopolysaccharidosis type Ⅰ (MPS Ⅰ ) is an autosomal recessive diseaseresulting from the deficiency in the lysosomal enzyme α-L-iduronidase (IDUA). The present study was conducted to identify IDUA gene mutations in attenuated (MPS Ⅰ H/S and MPS Ⅰ S) patients with MPS Ⅰin northern China. Methods Fourteen exons with adjacent intronic sequences of the IDUA gene in 11 MPS Ⅰ patients were amplified by polymerase chain reaction (PCR), and the PCR products were sequenced directly and origin analysis was conducted. Results Seven mutations were detected in the 11 MPS Ⅰ patients, i.e., c. 236 C>T(p. A79V), c. 266 G>A(p. R89Q), c. 265 C>T(p. R89W), c. 532G>A(p.E178K), c. 589G>A(p. G197S), c. 1037T>G(p. L346R), and c. 1877 G>A(p. W626X). All of them were known mutations. Six patients were homozygotes and 1 was heterozygote with nonsense mutation. In addition, 9 reported single nucleotide polymorphism (SNP) were detected, i. e., p. A8, p. A20, p. H33Q,p. R105Q, p. A314, p. A361T, p. T388, p. T410 and p. V454I. Conclusion The mutation spectrum of the IDUA gene in attenuated MPS Ⅰ Chinese patients may be different from that in patients from other countries. 相似文献
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目的研究粘多糖贮积症Ⅰ型(mucopolysaccharidosis type Ⅰ,MPS Ⅰ)患者发病的分子遗传学机理。方法采用聚合酶链产物直接测序的方法对患者的α-L-艾杜糖醛酸酶(alpha-L-iduronidase,IDUA)基因(仍删)外显子进行突变检测,并对发现的突变进行限制性酶切和等位基因特异性寡核苷酸杂交分析验证;同时,采集50名健康体检者血样,针对新发现的突变位点进行测序分析,以排除多态性位点的可能性。结果患者/DUA基因第2外显子和第6外显子分别出现杂合突变Q60X(178C〉T)和D203N(607G〉A),前者为已报道的无义突变,后者为新发现的错义突变。限制性酶切分析证实患者母亲是Q60X突变携带者,等位基因特异性寡核苷酸杂交分析证实患者父亲是D203N突变携带者。另外,在对50名正常人的测序分析中,未检测到D203N突变。结论筛查所得的两个点突变可能是患者的致病原因。 相似文献
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孙鲁宁 《国外医学:遗传学分册》2001,24(2):84-88
粘多糖贮积症Ⅰ型(MPS-Ⅰ)是由于溶酶体内α-L艾杜糖苷酶(IDUA)缺乏而引起的一种,常染色体隐性遗传病。IDUA基因定位于4p16.3,长约19kb,含14个外显子,迄今发现的IDUA基因突变达51种。突变在不同种族,不同民族的患中发生率不同。严重型突变基因的纯 合子引起MPS-ⅠH,轻型突变基因的纯合子引起MPS-ⅠS,严重型突变基因与轻型突变基因的杂合子引起MPS-ⅠH/S。 相似文献
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粘多糖贮积症Ⅱ型(MPSⅡ,OMIM 309900),是由于艾杜糖-2-硫酸酯酶(E.C.3.1.6.13)缺陷引起的一种遗传代谢病,国内发病率为1:132000男性。最近,我们对来自不同地区(四川、广东、云南)、不同民族(汉族、纳西族)的10多例疑是MPSⅡ的患儿进行了尿粘多糖(GAGs)含量检测和IDS基因突变分析,证实7例患儿患了此症。现报道如下。 相似文献
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本文对85 例无亲缘关系的广东汉人的170 例染色体进行IDUA 基因Kpn Ⅰ位点的RFLP研究,结果显示:等位基因A1 频率为0 .18 ,等位基因A2 频率为0.82,杂合率为32% 。经x2 检验,证实这些结果与国外报道的无显著性差异。对3个家系10 位成员等位基因传递规律的研究结果表明:A1 、A2 在世代中的传递完全符合孟德尔遗传规律。 相似文献
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Objective Mucopolysaccharidosis type Ⅰ (MPS Ⅰ ) is an autosomal recessive diseaseresulting from the deficiency in the lysosomal enzyme α-L-iduronidase (IDUA). The present study was conducted to identify IDUA gene mutations in attenuated (MPS Ⅰ H/S and MPS Ⅰ S) patients with MPS Ⅰin northern China. Methods Fourteen exons with adjacent intronic sequences of the IDUA gene in 11 MPS Ⅰ patients were amplified by polymerase chain reaction (PCR), and the PCR products were sequenced directly and origin analysis was conducted. Results Seven mutations were detected in the 11 MPS Ⅰ patients, i.e., c. 236 C>T(p. A79V), c. 266 G>A(p. R89Q), c. 265 C>T(p. R89W), c. 532G>A(p.E178K), c. 589G>A(p. G197S), c. 1037T>G(p. L346R), and c. 1877 G>A(p. W626X). All of them were known mutations. Six patients were homozygotes and 1 was heterozygote with nonsense mutation. In addition, 9 reported single nucleotide polymorphism (SNP) were detected, i. e., p. A8, p. A20, p. H33Q,p. R105Q, p. A314, p. A361T, p. T388, p. T410 and p. V454I. Conclusion The mutation spectrum of the IDUA gene in attenuated MPS Ⅰ Chinese patients may be different from that in patients from other countries. 相似文献
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Objective Mucopolysaccharidosis type Ⅰ (MPS Ⅰ ) is an autosomal recessive diseaseresulting from the deficiency in the lysosomal enzyme α-L-iduronidase (IDUA). The present study was conducted to identify IDUA gene mutations in attenuated (MPS Ⅰ H/S and MPS Ⅰ S) patients with MPS Ⅰin northern China. Methods Fourteen exons with adjacent intronic sequences of the IDUA gene in 11 MPS Ⅰ patients were amplified by polymerase chain reaction (PCR), and the PCR products were sequenced directly and origin analysis was conducted. Results Seven mutations were detected in the 11 MPS Ⅰ patients, i.e., c. 236 C>T(p. A79V), c. 266 G>A(p. R89Q), c. 265 C>T(p. R89W), c. 532G>A(p.E178K), c. 589G>A(p. G197S), c. 1037T>G(p. L346R), and c. 1877 G>A(p. W626X). All of them were known mutations. Six patients were homozygotes and 1 was heterozygote with nonsense mutation. In addition, 9 reported single nucleotide polymorphism (SNP) were detected, i. e., p. A8, p. A20, p. H33Q,p. R105Q, p. A314, p. A361T, p. T388, p. T410 and p. V454I. Conclusion The mutation spectrum of the IDUA gene in attenuated MPS Ⅰ Chinese patients may be different from that in patients from other countries. 相似文献
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本文对85例无亲缘关系的广东汉人的170例染色体进行IDUA基因KpnⅠ位点的RFLP研究,结果显示:等位基因A1频率为0.18,等位基因A2频率为0.82,杂合率为32%。经x^2检验,证实这些结果与国外报宾无显著性差异。对3个家系10位成员等位基因传递规律的研究结果表明:A1、A2在世代中的传递完全符合孟德尔遗传规律。 相似文献
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建立了微量测定芳基硫酸酯酶B活性的方法。对二例粘多糖贮积症Ⅵ型进行病例诊断,并对其中一个家系的高危孕妇于孕中期进行产前诊断,结果判断胎儿正常,婴儿出生后验证正常。 相似文献
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粘多糖贮积症ⅣA 型(MPSⅣA)是由于溶酶体内N乙酰半乳糖胺6硫酸酯酶(GALNS)缺乏而引起的一种常染色体隐性遗传病(AR)。对MPSⅣA 的研究近年来取得了重大进展。本文就MPSⅣA 的发病机理、GALNS基因结构、基因变异类型以及基因诊断的最新进展作一综述。 相似文献
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粘多糖贮积症ⅣA的分子遗传学研究进展 总被引:1,自引:0,他引:1
郭奕斌 《国外医学:遗传学分册》1999,22(4):173-179
粘多糖贮积症ⅣA型是由于溶酶体内N-乙酰半乳糖胺6-硫酸酯酶缺乏而引起的一种常染色体隐性遗传病。对MPSⅣ的研究近年来取得了重大进展。本就MPSⅣA的发病机理,GALNS基因,基因变异类型以及基因诊断的最新进展作一综述。 相似文献
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粘多糖贮积症Ⅱ型患者IDS基因的一个新突变 总被引:3,自引:1,他引:3
目的 研究粘多糖贮积症 型 ( mucopolysaccharidosis type ,MPS )患者的艾杜糖 - 2 -硫酸酯酶 ( iduronate- 2 - sulfatase,IDS)基因的基因突变。方法 应用聚合酶链反应 -单链构象多态性( polymerase chain reaction- single strand conformation polymorphism,PCR- SSCP)对患者的 IDS基因可能的常见突变第 2、3、5、7~ 9外显子进行检测 ,并对 PCR- SSCP检出的突变进行直接测序 ,测序发现的突变进行 PCR-限制性酶切分析验证。结果 经 PCR- SSCP和 DNA序列分析发现该患者的第 7外显子发生新的点突变 ( G12 5 3T) ;聚合酶链反应 -限制性片段长度多态性 ( PCR- RFL P)电泳检测示患者和母亲出现突变导致的酶切位点 ,进一步验证了序列分析结果。结论 筛查所得的点突变 G12 5 3T可能是该 MPS 患者的致病原因 相似文献
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粘多糖贮积症Ⅱ型患者艾杜糖-2-硫酸酯酶基因常见突变的检测 总被引:4,自引:1,他引:4
目的 探讨并建立粘多糖贮积症Ⅱ型(mucopolysaccharidosis Ⅱ,MPSⅡ)患者艾杜糖-2-硫酸酯酶(iduronate-2-sulphatase,IDS)基因常见突变的检测方法。方法 应用聚合酶链反应-单链构象多态性(polymerase chain reaction-single strand conformation polymorphism,PCR-SSCP)对IDS基因突变热点外显子3、8和9进行点突变检测;应用DNA测序对PCR-SSCP检出的突变进行序列分析;应用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)对DNA测序的结果进行检测。结果 以PCR-SSCP发现该患者的IDS基因外显子9有明显异常泳动的条带;DNA测序发现患儿的外显子9发生点突变(C1672T),从而导致患者艾杜糖-2-硫酸酯酶蛋白发生氨基酸替换(R468W);PCR-RFLP电泳检测结果显示粘多糖贮积症Ⅱ型患者仅出现554bp 1条带,而患儿父母出现257bp和297bp 2条带,进一步验证了序列分析的结果。结论 PCR-SSCP分析、DNA序列分析和PCR-RFLP分析是诊断MPSⅡ的有效方法,三者联合使用可以相互验证、互为补充,提高基因诊断的准确率和成功率。 相似文献
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