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
Mucopolysaccharidosis type II is of high ge-netic heterogeneity. PCR-DNA sequencing was used to study the mutation hot spots in the IDS gene of a Chinese MPS II pedigree. A new mutation (1467-A) not yet reported world...Mucopolysaccharidosis type II is of high ge-netic heterogeneity. PCR-DNA sequencing was used to study the mutation hot spots in the IDS gene of a Chinese MPS II pedigree. A new mutation (1467-A) not yet reported world-wide was detected. This mutation located at 448th codon in the coding region of exon 9 deletes one “A” at the end of 1467 bp (cDNA). The frame-shift mutation makes the peptide chain shorten from amino acids 550 to 459, probably altering the configuration of IDS enzyme protein remarkably and lowering the activation of IDS greatly. Therefore it is sup-posed to be the direct cause of the patient with MPS II and to be a necessary premise for prenatal gene diagnosis.展开更多
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，采用PCR扩增艾杜糖-2-硫酸酯酶（IDS）基因突变热点区（外显子2、3、5、7、8和9）、DNA测序分析和限制性内切酶图谱分析的方法，对2个粘多糖贮积症Ⅱ型家系进行了遗传突变...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，采用PCR扩增艾杜糖-2-硫酸酯酶（IDS）基因突变热点区（外显子2、3、5、7、8和9）、DNA测序分析和限制性内切酶图谱分析的方法，对2个粘多糖贮积症Ⅱ型家系进行了遗传突变分析。结果表明，2个家系患者的IDS基因分别出现IVS6-1g→a和c．1587～1588 ins T2个新突变。前者属于单碱基替换，位于内含子6的3’端剪接位点，导致跨外显子剪接；后者属于插入突变，插入点位于外显子9的cDNA1，587和1，588碱基之间，是迄今为止报道的人类IDS基因插入突变中最接近肽链末端的突变，导致移码突变和转录提前终止。经限制性酶切分析，证实2个家系中的患者母亲是突变基因的携带者，符合该病X染色体隐性遗传的规律。另外，在对随机抽取的50名正常人及另外6名不相关的粘多糖病人的测序分析中，未检测到这2个突变，说明不是多态性。对于筛查所得的2个新突变是否是患者的致病原因，尚需进一步证实。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Mucopolysaccharidosis type II is of high ge-netic heterogeneity. PCR-DNA sequencing was used to study the mutation hot spots in the IDS gene of a Chinese MPS II pedigree. A new mutation (1467-A) not yet reported world-wide was detected. This mutation located at 448th codon in the coding region of exon 9 deletes one “A” at the end of 1467 bp (cDNA). The frame-shift mutation makes the peptide chain shorten from amino acids 550 to 459, probably altering the configuration of IDS enzyme protein remarkably and lowering the activation of IDS greatly. Therefore it is sup-posed to be the direct cause of the patient with MPS II and to be a necessary premise for prenatal gene diagnosis.
文摘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，采用PCR扩增艾杜糖-2-硫酸酯酶（IDS）基因突变热点区（外显子2、3、5、7、8和9）、DNA测序分析和限制性内切酶图谱分析的方法，对2个粘多糖贮积症Ⅱ型家系进行了遗传突变分析。结果表明，2个家系患者的IDS基因分别出现IVS6-1g→a和c．1587～1588 ins T2个新突变。前者属于单碱基替换，位于内含子6的3’端剪接位点，导致跨外显子剪接；后者属于插入突变，插入点位于外显子9的cDNA1，587和1，588碱基之间，是迄今为止报道的人类IDS基因插入突变中最接近肽链末端的突变，导致移码突变和转录提前终止。经限制性酶切分析，证实2个家系中的患者母亲是突变基因的携带者，符合该病X染色体隐性遗传的规律。另外，在对随机抽取的50名正常人及另外6名不相关的粘多糖病人的测序分析中，未检测到这2个突变，说明不是多态性。对于筛查所得的2个新突变是否是患者的致病原因，尚需进一步证实。
