中国人D13S301位点的微卫星多太及其应用价值

率先在国内应用ＰＣＲ技术扩增Ｗｉｌｓｏｎ病（ＷＤ）基因内部Ｄ１３Ｓ３０１位点的微卫星多态，通过变性聚丙烯酰胺凝胶电泳检测扩增产物，对８０名正常中国人进行了检测，结果具有１２种不同长度的等位片段，多态信息含量（ＰＩＣ值）为０．８８３，表明该位点在中国人群中具有长度多态性及较高的应用价值。应用该位点对１０个ＷＤ家系进行连锁分析，在２４名无症状个体中检出１２名基因携带者，７名正常纯合子及２名症状前患     

中国人D13S301位点多态性及Wilson病基因诊断的研究

Ｗｉｌｓｏｎ病 (Ｗｉｌｓｏｎｄｉｓｅａｓｅ ,ＷＤ)的有效防治有赖于ＷＤ的早期诊断、症状前诊断及杂合子检测。微卫星ＤＮＡ (ｓｈｏｒｔｔａｎｄｅｍｒｅｐｅａｔ,ＳＴＲ)Ｄ13Ｓ30 1是ＷＤ基因内ＳＴＲ。我们应用聚合酶链反应 (ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎ ,ＰＣＲ)扩增片段长度多态性 (ａｍｐｌｉｆｉｅｄｆｒａｇｍｅｎｔｌｅｎｇｔｈｐｏｌｙｍｏｒｐｈｉｓｍ ,Ａｍｐ ＦＬＰ)技术分析国人Ｄ13Ｓ30 1位点的多态性分布 ,探讨Ｄ13Ｓ30 1与ＷＤ基因位点 (ＷＮＤ)的连锁关系 ,并对 12个ＷＤ家系进行基因诊断。资料和…     

Wilson病与微卫星DNA的连锁分析

目的探索国人Ｗｉｌｓｏｎ病（ＷＤ）基因位点（ＷＮＤ）与ＡＦＭ２３８ｖｃ３、Ｄ１３Ｓ３０１、Ｄ１３Ｓ３１６、Ｄ１３Ｓ２９６、及ＡＦＭ０８４ｘｃ５等５个微卫星ＤＮＡ（ＳＴＲ）之连锁关系，对ＷＮＤ进行精确定位。为ＷＤ基因克隆奠定基础。方法对２０个ＷＤ家系１１３名成员及１００名正常对照组成员的ＤＮＡ进行５个ＳＴＲ的聚合酶链反应（ＰＣＲ）扩增片段长度多态性分析；对ＷＮＤ及５个ＳＴＲ进行二点配对及多点连锁分析。结果ＷＮＤ与Ｄ１３Ｓ３０１、Ｄ１３Ｓ３１６、Ｄ１３Ｓ２９６呈紧密连锁，与ＡＦＭ２３８ｖｃ３及ＡＦＭ０８４ｘｃ５呈中度连锁。结论ＷＮＤ与５个ＳＴＲ的遗传连锁图谱为：着丝点—ＡＦＭ２３８ｖｃ３—Ｄ１３Ｓ３０１—ＷＮＤ—Ｄ１３Ｓ３１６—Ｄ１３Ｓ２９６—ＡＦＭ０８４ｘｃ５—端粒     

中国人D13S316位点CA重复序列的多态性分析

应用ＰＣＲ方法扩增Ｄ１３Ｓ３１６位点的ＣＡ重复序列，通过变性聚丙烯酰胺凝胶电泳检测扩增产物，测定了８０名正常人人的多态频率，结果得到９种不同的等位片ＰＩＣ值为０．８０，表明该位点经中国人群中具有长度多态性；正常家系连锁结果呈孟得尔分离，在此，可用于Ｗｉｌｓｏｎ病家第的基因诊断。     

中国南方汉人D13S316位点多态性及Wilson病基因诊断的研究

目的　评估中国南方汉人Wilson病 (WD)基因 (WND)侧翼微卫星DNA(STR)位点D13S3 16的基因多态性及在WD基因诊断中的价值。方法　采用聚合酶链反应 (PCR)、变性聚丙烯酰胺凝胶电脉和银染法分析 84名无血缘关系中国南方汉人D13S3 16的片段长度多态性 ;并对 19个WD家系进行STR连锁分析。结果　D13S3 16有 19个等位片段 ,长度范围为 13 4～ 170bp ,多态信息含量 (PIC)为 0 93 1。共检出 8例症状前患者 ,10例致病基因携带者及 15例正常人 ,3例未能确定 ,基因诊断率达 91 67%。结论　D13S3 16大致代表中国南方汉人的多态性标记 ,对WD基因诊断有重要价值。     

WD基因内部及其两侧翼的微卫星多态快速检出Wilson＇s病基因携带者及症状前患者

Ｗｉｌｓｏｎ＇ｓ病（ＷＤ）的杂合子检识及症状前诊断是临床上的两大难题。本研究率先在国内应用多聚酶链式反应方法扩增ＷＤ基因内部及其两侧翼的微卫星多态－Ｄ１３５３０１、Ｄ１３Ｓ１３３和Ｄ１３Ｓ３１４，对１２个ＷＤ家系的８２名成员进行单体型连锁分析，判断出２５名肯定携带者，１８名正常纯合子及２名症状前患者，弥补了临床及生化诊断的不足，为ＷＤ的基因诊断提供了重要的新手段。     

中国人Wilson病患者基因高频突变位点的快速检测

果均经DNA测序证实.结论 13外显子Pm992Leu突变是中国人WD患者的基凶突变热点之一.采用限制性酶谱分析法能快速、准确检出WD患者基因高频突变位点,可用于对WD疑诊患者及其家系成员的基因诊断.     

Ⅰ型神经纤维瘤病微卫星DNA在中国人中的多态性

目的　为了评估中国人Ⅰ型神经纤维瘤病 (NF1)基因内微卫星ALU、IVS3 8GT5 3 0、EVI2 0CA、IVS2 7GT2 8 4的基因多态性及在基因诊断中的价值。方法　应用聚合酶链反应 (PCR) ,变性聚丙烯凝胶电泳 (PAGE)和银染法分析 112名无血缘关系的中国南方汉人的片段长度多态性。结果　ALU的信息含量 (PIC)为 0 3 12 ,共有 4种等位片段 ;IVS3 8GT5 3 0有 9种等位片段 ,PIC为 0 782 ;EVI2 0CA有 10种等位片段 ,PIC为 0 83 5 ;IVS2 7GT2 8 4的PIC为 0 814 ,有 14种等位片段。结论　研究人群与文献报道的白种人群相比 ,这四种微卫星在种类和分布上有差异 ;IVS3 8GT5 3 0 ,EVI2 0CA ,IVS2 7GT2 8 4是高度多态的遗传标记 ,可用于NF1的连锁基因诊断、法医学的个体鉴定和亲权鉴定。     

应用D13S296位点多态性对肝豆状核变性家系的基因诊断

目的 评估中国人群肝豆状核变性基因（ＷＮＤ）侧翼微卫星ＤＮＡ（ＳＴＲ）位点Ｄ１３Ｓ２９６的基因多态性及在ＷＤ基因诊断中的价值。方法 采用聚合酶链反应（ＰＣＲ）,变性聚丙烯酰胺凝胶电泳和银染法分析９８名无血缘关系中国人Ｄ１３Ｓ２９６的片段长度多态性,并对１９个ＷＤ家系进行ＳＴＲ连锁分析。结果 Ｄ１３Ｓ２９６有１８个等位片段,长度范围为１０６－１４０ｂｐ,多态信息含量（ＰＩＣ）为０．９０６。共检出８例     

微卫星D6S1960和D6S274多态性与精神分裂症的关联研究

目的探讨江西地区汉族人群微卫星D6S1960和D6S274遗传多态性与精神分裂症的关系。方法对符合美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准的174例精神分裂症患者进行微卫星D6S1960和D6S274多态性的检测,以174名健康体检者为正常对照组。结果患者组和正常对照组D6S1960位点的273bp等位基因的检出率分别为21.55%(75/348)和11.78%(41/348),两者的差异有统计学意义(X2=11.93,P0.01);两组D6S274位点的172bp等位基因检出率分别为11.78%(41/348)和4.60%(16/348),差异也有统计学意义(X2=11.93,P0.01)。两组间其他等位基因的检出率差异无统计学意义(P0.05)。结论 6号染色体短臂D6S1960和D6S274附近可能存在精神分裂症的易感基因。     

Frequency of His1069Gln and Gly1267Lys mutations in Polish Wilson's Disease population

Wilson's disease is an autosomal recessive disorder. More than 60 mutations of the Wilson's disease gene have been described so far. We have analysed 148 Polish Wilson's disease patients from 95 families for His1069Gln and Gly1267Lys mutations and correlated this finding with age and clinical form of the disease at presentation. To identify these mutations, single strand conformation polymorphism analysis was performed. In our group there were 94 patients with neurological presentation, 28 with hepatic presentation, whilst 26 were in a pre-clinical stage of the disease. His1069Gln mutation was present on 171 (57%) of the 296 studied chromosomes, and Gly1267Lys mutation was present on 27 chromosomes (9.1%). Most of our patients were homozygous or heterozygous for His1069Gln mutation (39.9% and 30.4%, respectively); 4% of the patients were homozygous for Gly1267Lys mutation and 5.4% had both of these described mutations on their chromosomes. His1069Gln and Gly1267Lys mutations occurred often in our Wilson's disease patient population but we did not find any relationship between investigated mutations and the clinical form of Wilson's disease or age of first symptoms.     

Central Pontine Signal Changes in Wilson's Disease: Distinct MRI Morphology and Sequential Changes with De-Coppering Therapy

BACKGROUND AND PURPOSE: Reports of central pontine myelinolysis (CPM)-like changes in Wilson's disease (WD) and its sequential changes are exceptional. The aim was to study the MRI characteristics of CPM-like changes in WD and the serial changes. METHODS: Among the 121 patients of WD, twenty (M:F:9:11, age at onset: 14.2 +/- 4.6 years) had features similar to CPM. All had progressive neuropsychiatric form of WD. All except five were on de-coppering treatment. None had acute deterioration or hepatic failure. Ten patients underwent repeat studies. RESULTS: Twenty patients with CPM-like changes manifested with characteristic phenotype of WD. Three distinct patterns of CPM-like changes were observed: (a) characteristic round shape -7, (b) "bisected" -9, and (c) "trisected" -4. Only one had signal changes suggesting extra-pontine myelinolysis. All patients had contiguous involvement of midbrain. Serial MRI evaluation in 10 patients, at mean interval period of 17.4 +/- 13.2 months, revealed complete reversal in one, partial improvement in five, and no change in three. Clinical and MRI improvement occurred pari passu, except in one. CONCLUSIONS: CPM-like changes in WD are perhaps under-recognized and are distinct from the commonly known "osmotic demyelination." It is potentially reversible similar to other MRI features of WD.     

中文版统一肝豆状核变性评分量表的信度和效度的研究

目的 研究中文版统一肝豆状核变性评分量表(UWDRS)的信度和效度.方法 采用翻译和回译将UWDRS翻译为中文版本.应用中文版UWDRS评价110例肝豆状核变性(HLD)患者,评价其信度和效度.结果 中文版UWDRS量表总分为31.27(20.656,0～89),神经功能得分为17.53(15.867,0～64),肝脏功能得分为6.46(6.150,0～ 36),精神症状得分为7.27 (6.045,0～ 26).量表整体Cronbach α系数为0.967,神经功能为0.975、肝脏功能为0.493、精神症状为0.798.总量表Spearman-Brown系数为0.811,神经功能为0.941,肝脏功能为0.392,精神症状为0.775.总量表2次测定的重测相关系数为0.968,神经功能为0.970、肝脏功能为0.628、精神症状得分为0.823(均P＜0.001);总量表的两位评定者间相关系数为0.920,神经功能为0.927,肝脏功能为0.584,精神症状得分为0.676(均P＜0.001).结构效度没有只出现3个明确的因子,但有6个因子解释了总变异的50.685％.总量表的平均量表水平内容效度指数(S-CVI/Ave)值为0.99.结论 中文版UWDRS具有良好的信度和效度,但部分内容尚需进一步修订.     

Wilson's Disease with Extensive Degeneration of Cerebral White Matter and Cortex

Abstract: This is a report of an autopsy case of Wilson's disease with widespread degeneration of the cerebral cortex and white matter, the basal ganglia and thalamus and, to a lesser degree, the cerebellum and brain stem. The patient was a 28-year-old man at the time of death with the clinical course of a 20-year duration.
The lesions consisted of spongy degeneration leading to a cavity formation with insufficient glia fiber proliferation. We noted the characteristic findings of Alzheimer glia (Types I and II) and Opalski cells and the new formation in capillaries.
The distribution of the changes in the hemispheres showed the typical pattern with a tendency of preferential superior and anterior localization and a relative preservation of the hippocampal formation, carcarine areas, amygdaloid nuclei and the hypothalamus.
Similar cases in the literature were reviewed.     

Dopamine D2 receptor binding and cerebral glucose metabolism recover afterd-penicillamine-therapy in Wilson's disease

Regional cerebral glucose metabolism (rCMRGlc) and dopamine D2 receptor binding were measured in a 31-year-old, severely affected, untreated patient with Wilson's disease of 3 years' duration using positron emission tomography and¹⁸F-deoxyglucose and¹⁸F-methylspiperone ([¹⁸F]MSP), respectively. There was a severe reduction of striatal and extrastriatal rCMRGlc as well as of striatal [¹⁸F]MSP accumulation rate. After 1 year of treatment withd-penicillamine, striatal and extrastriatal rCMRGlc and striatal [¹⁸F]MSP accumulation rate reached almost normal levels. It is hypothesized that recovery of motor functions due to copper trapping therapy was associated with an increase in basal ganglia activity and a re-expression or upregulation of dopamine D2 receptors.     

锌孵育对肝豆状核变性离体培养细胞内铜、锌和金属硫蛋白代谢的影响

本实验研究了锌孵育后肝豆状核变性患者和杂合子离体培养皮肤成纤维细胞内铜、锌和金属硫蛋白（ＭＴ）代谢的改变，以及经４５．８８μｍｏｌ／Ｌ锌孵育后，患者胞浆内钢含量增高，同时ＭＴ上的钢结合量也增高，但ＭＴ含量无明显变化，根据上述结果，对锌剂治疗本病的作用机理进行了初步讨论。     

Dopamine D2 receptor binding is reduced in Wilson's disease: Correlation of neurological deficits with striatal123I-Iodobenzamide binding

Summary To visualise and quantify dopamine D2 receptor binding in the corpus striatum of patients with neurological Wilson's disease (WD) 123I-Iodobenzamide (IBZM) binding was measured using single photon emission computer tomography (SPECT). Ratios of striatal to frontal countrates were calculated in 8 patients and in 21 healthy control subjects. We found reduced IBZM binding ratios in all patients with WD in comparison to those in controls (1.48 +- 0.13 vs. 1.73 +- 0.09). The reduction in IBZM binding was correlated with the overall severity of neurological deficits and the severity of dysarthria (correlation coefficients –0.86 [p < 0.01] and –0.79 [p s< 0.01], respectively). When patients of three different subgroups of neurological WD were compared no differences in IBZM binding were found. We conclude that assessing basal ganglia function in vivo using IBZM-SPECT is a valuable diagnostic tool in WD.     

1200例肝豆状核变性的肝脾胆肾声像图表现及临床研究

目的:探讨肝豆状核变性的肝、脾、胆、肾声像图改变与临床表现的关系。方法:对1200例患者行腹部超声检查,并与临床资料进行对比分析。结果:肝脏声像图1200例均有异常(100％),主要表现为回声光点增多、增粗、增强,其改变可分为7型;脾脏肿大939例(79.8％);慢性胆囊炎253例(21.1％),胆囊壁水肿107例(8.9％),胆石症64例(5.3％);肾脏皮质回声增粗、增强515例(42.9％);腹水120(10.0％)。肝脏声像图各型的临床表现组间对比有显著差异(P<0.01)。结论:本病患者腹部声像图异常表现的发生率较高,对声像图有上述异常的青少年患者,可检查有无角膜K-F环和铜代谢异常,以免漏诊。     

Comparison of clinical types of Wilson's disease and glucose metabolism in extrapyramidal motor brain regions

In Wilson's disease a disturbed glucose metabolism especially in striatal and cerebellar areas has been reported. This is correlated with the severity of extrapyramidal motor symptoms (EPS). These findings are only based on a small number of patients. Up to now it is unknown whether EPS are caused by various patterns of disturbed basal ganglia glucose metabolism. We investigated 37 patients and 9 normal volunteers to characterize the disturbed glucose metabolism in Wilson's disease more precisely. The glucose metabolism was determined in 5 cerebellar and cerebral areas (putamen, caput nuclei caudati, cerebellum, midbrain and thalamic area) by using ¹⁸ F-Fluorodesoxyglucose-Positron-Emission-Tomography ( [ ¹⁸ F]FDG-PET). The database was evaluated by a cluster analysis. Additionally, the severity extrapyramidal motor symptoms were judged by a clinical score system. Three characteristic patterns of glucose metabolism in basal ganglia were obtained. Two of them may be assigned to patients with neurological symptoms whereas the third cluster corresponds to most patients without EPS or normal volunteers. The clusters can be identified by characteristic consumption rates in this 5 brain areas. The severity of EPS can not clearly be assigned to one of the clusters with disturbed glucose metabolism. However, the most severe cases are characterized by the lowest consumption in the striatal area. When there is marked improvement of EPS impaired glucose consumption reveals a persistent brain lesion. Finally, the neurological symptoms in Wilson's disease are caused by (at least) two different patterns of disturbed glucose metabolism in basal ganglia and cerebellum. The severity of EPS seems to be determined by a disturbed consumption in the striatal area. Received: 6 July 2001, Received in revised form: 14 November 2001, Accepted: 3 December 2001