Background:Mucopolysaccharidosis(MPS)diseases lead to a profound disruption in normal mechanisms of growth and development.This study was undertaken to determine the general growth of children with MPS I and II.Method...Background:Mucopolysaccharidosis(MPS)diseases lead to a profound disruption in normal mechanisms of growth and development.This study was undertaken to determine the general growth of children with MPS I and II.Methods:The anthropometric data of patients with MPS I and II(n=76)were retrospectively analyzed.The growth patterns of these patients were analyzed and then plotted onto Polish reference charts.Longitudinal analyses were performed to estimate age-related changes.Results:At the time of birth,the body length was greater than reference charts for all MPS groups(Hurler syndrome,P=0.006;attenuated MPS II,P=0.011;severe MPS II,P<0.001).The mean z-score values for every MPS group showed that until the 30th month of life,the growth patterns for all patients were similar.Afterwards,these growth patterns start to differ for individual groups.The body height below the 3rd percentile was achieved around the 30th month for boys with Hurler syndrome,between the 4th and 5th year for patients with severe MPS H and between the 7th and 8th year for patients with attenuated MPS H.Conclusions:The growth pattern differs between patients with MPS I and H.It reflects the clinical severity of MPS and may assist in the evaluation of clinical efficacy of available therapies.展开更多
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...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。展开更多
目的对两个粘多糖贮积症Ⅰ型（mucopolysaccharidosis type Ⅰ ,MPS Ⅰ）家系α—L-艾杜糖醛酸酶（α—L—iduronidase，IDUA）基因进行基因突变分析，为家系中的高危胎儿提供产前诊断。方法应用PCR扩增和直接双向测序分别对两个粘多糖...目的对两个粘多糖贮积症Ⅰ型（mucopolysaccharidosis type Ⅰ ,MPS Ⅰ）家系α—L-艾杜糖醛酸酶（α—L—iduronidase，IDUA）基因进行基因突变分析，为家系中的高危胎儿提供产前诊断。方法应用PCR扩增和直接双向测序分别对两个粘多糖贮积症Ⅰ型家系的先证者及其父母IDUA基因的14个外显子进行基因突变分析。基因突变确定后，抽取绒毛样本对家系胎儿进行产前诊断。结果测序结果显示家系1先证者存在IDUA基因第1外显子c．46-57delTCGCTCCTGGCC（p．Ser16_Ala19del）和第8外显子c．1147delC（p．Arg383Alafs＊57）复合杂合突变，先证者父亲为c．46—57delTCGCTCCTGGCC杂合突变携带者，先证者母亲为c．1147delC杂合突变携带者，先证者两个突变分别来自父母，前者为已知突变、后者为未报道过的新突变；产前诊断显示胎儿携带c．46—57delTcGcTccTGGc杂合缺失突变。家系2先证者存在IDUA基因第6外显子c．721T〉C（p．Cys241Arg）和第10外显子c．1491delG（p．Thr497fs27）复合杂合突变；先证者母亲为c．721T〉C错义杂合突变携带者，父亲为c．1491delG缺失杂合突变携带者，先证者的两个突变分别来自父母，均为未报道过的新突变，产前诊断显示胎儿携带c．721T〉C杂合错义突变。结论IDUA基因突变是2个粘多糖贮积症Ⅰ型家系的致病原因，我们的结果丰富了IDUA基因突变谱，为家系产前诊断提供了依据。展开更多
文摘Background:Mucopolysaccharidosis(MPS)diseases lead to a profound disruption in normal mechanisms of growth and development.This study was undertaken to determine the general growth of children with MPS I and II.Methods:The anthropometric data of patients with MPS I and II(n=76)were retrospectively analyzed.The growth patterns of these patients were analyzed and then plotted onto Polish reference charts.Longitudinal analyses were performed to estimate age-related changes.Results:At the time of birth,the body length was greater than reference charts for all MPS groups(Hurler syndrome,P=0.006;attenuated MPS II,P=0.011;severe MPS II,P<0.001).The mean z-score values for every MPS group showed that until the 30th month of life,the growth patterns for all patients were similar.Afterwards,these growth patterns start to differ for individual groups.The body height below the 3rd percentile was achieved around the 30th month for boys with Hurler syndrome,between the 4th and 5th year for patients with severe MPS H and between the 7th and 8th year for patients with attenuated MPS H.Conclusions:The growth pattern differs between patients with MPS I and H.It reflects the clinical severity of MPS and may assist in the evaluation of clinical efficacy of available therapies.
文摘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。
文摘目的对两个粘多糖贮积症Ⅰ型（mucopolysaccharidosis type Ⅰ ,MPS Ⅰ）家系α—L-艾杜糖醛酸酶（α—L—iduronidase，IDUA）基因进行基因突变分析，为家系中的高危胎儿提供产前诊断。方法应用PCR扩增和直接双向测序分别对两个粘多糖贮积症Ⅰ型家系的先证者及其父母IDUA基因的14个外显子进行基因突变分析。基因突变确定后，抽取绒毛样本对家系胎儿进行产前诊断。结果测序结果显示家系1先证者存在IDUA基因第1外显子c．46-57delTCGCTCCTGGCC（p．Ser16_Ala19del）和第8外显子c．1147delC（p．Arg383Alafs＊57）复合杂合突变，先证者父亲为c．46—57delTCGCTCCTGGCC杂合突变携带者，先证者母亲为c．1147delC杂合突变携带者，先证者两个突变分别来自父母，前者为已知突变、后者为未报道过的新突变；产前诊断显示胎儿携带c．46—57delTcGcTccTGGc杂合缺失突变。家系2先证者存在IDUA基因第6外显子c．721T〉C（p．Cys241Arg）和第10外显子c．1491delG（p．Thr497fs27）复合杂合突变；先证者母亲为c．721T〉C错义杂合突变携带者，父亲为c．1491delG缺失杂合突变携带者，先证者的两个突变分别来自父母，均为未报道过的新突变，产前诊断显示胎儿携带c．721T〉C杂合错义突变。结论IDUA基因突变是2个粘多糖贮积症Ⅰ型家系的致病原因，我们的结果丰富了IDUA基因突变谱，为家系产前诊断提供了依据。
