BACKGROUND： ATP7B gene exon 8 Arg778Leu and exon 12 Arg952Lys are gene mutation hot spots in Chinese Han patients with hepatolenticular degeneration, or Wilson＇s disease （WD）. However, the gene fragments are too s...BACKGROUND： ATP7B gene exon 8 Arg778Leu and exon 12 Arg952Lys are gene mutation hot spots in Chinese Han patients with hepatolenticular degeneration, or Wilson＇s disease （WD）. However, the gene fragments are too short for detection and the mutation detection rate remains low. OBJECTIVE： To analyze DNA sequences of ATP7B gene exon 8-exon 9 and exon 10-exon 12 sections. DESIGN, TIME AND SE＇I-rlNG： A concurrent, non-randomized, controlled, genetic polymorphism study was performed at the Anhui Medical Genetics Center, Anhui, China from March to July in 2009. PARTICIPANTS： Fifty patients, who were admitted to the Department of Neurology at the First Affiliated Hospital of Anhui Traditional Chinese Medical College between March and July in 2009, were diagnosed with WD. The WD group comprised 32 males and 18 females, with an average age of （18.8 ± 8.3） years. WD was confirmed by clinical observation, as well as physical, imaging, and biochemical examinations, including testing for serum copper, ceruloplasmin, and copper oxidase. The control group comprised 20 normal subjects, who underwent physical examination at the First Affiliated Hospital of Anhui Traditional Chinese Medical College, and included 13 males and 7 females, with an average age of （27.9 ± 2.4） years. All subjects were Chinese Han population. METHODS： Genomic DNA was extracted from 50 WD patients and 20 normal controls. Polymerase chain reaction amplification of ATP7B gene exon 8-exon 9 （about 1 100 bp） and exon 10-exon 12 （about 850 bp） segments was performed. DNA exon-intron amplification products from all subjects were processed through direct bidirectional sequencing, and sequencing results were analyzed. MAIN OUTCOME MEASURES： Sequence changes of ATPTB gene exon 8-exon 9 and exon 10-exon 12 segments. RESULTS： In the 50 included WD patients, ATP7B gene intron 8 nt53592A → G with nt53671G→ A homozygous mutation was detected between exon 8-exon 9 in seven cases; exon 8 Arg778Leu mutations with Leu770Leu synonymous mutation was detected in four cases; exert 11 Gly790Arg heterozygous missense mutation between exon 10-exon 12 was found in four cases; exon 12 Arg952Lys heterozygous missense mutation was seen in 11 cases; and two additional cases were associated with exon 1211e929Val polymorphism. CONCLUSION： ATP7B gene intron 8 mutation is a possible pathogenic mutation that is associated with WD pathogenesis. The exon 11 mutation rate accounts for 8% of all WD patients, and the very few previously reported cases deserve further study.展开更多
本文简要介绍第九届国际帕金森病暨运动障碍疾病研讨会及中国卒中学会移动医学上海论坛的学术内容。会议在2023年6月8日—10日在上海召开,世界神经病学争议大会会务组核心团队支持,由上海交通大学医学院附属第一人民医院及其嘉定分院主...本文简要介绍第九届国际帕金森病暨运动障碍疾病研讨会及中国卒中学会移动医学上海论坛的学术内容。会议在2023年6月8日—10日在上海召开,世界神经病学争议大会会务组核心团队支持,由上海交通大学医学院附属第一人民医院及其嘉定分院主办。王晓平、Amos D Korczyn和赵钢教授担任大会主席,来自巴基斯坦、以色列、美国、希腊和瑞典等国家近10位知名专家通过Zoom视频软件进行会议演讲,就帕金森病、脑血管病、癫痫、偏头痛、肝豆状核变性等罕见病进行了广泛的学术交流,并展开了类似世界神经病学争议大会的热烈讨论和辩论,邀请了多位专业的双语(英语⁃中文)同步翻译,取得了很好的交流效果,吸引了国际上超过30000人次以上的观众和听众来收看和收听。展开更多
目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总...目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总分>50分界定为具有网络成瘾倾向;使用Barratt冲动量表中文版(the Chinese version of the Barratt impulsiveness scale,11version,BIS-11-C)评估患者冲动性;手机依赖量表(mobile phone addiction index,MPAI)评估对手机使用的依赖程度;通过颅脑MRI检查患者病变脑区的部位和累计频次。结果66例WD患者中有数字成瘾倾向者45例(68.2%),其中脑型组中35例(53.0%)、肝型组中10例(15.2%),两组成瘾倾向者比例差异有统计学意义(P=0.001)。脑型组患者在BIS-11-C、MPAI量表多项因子分上高于肝型组(P<0.05)。所有患者MPAI量表中失控性因子分与BIS-11-C量表中的注意力冲动性因子分(r=0.499,P=0.001)、运动冲动性因子分(r=0.553,P=0.001)、无计划冲动性因子分(r=0.535,P=0.001)、冲动控制总分(r=0.653,P=0.001)正相关。线性回归分析显示注意力冲动性因子分与额叶病变(B=-1.634,P=0.018)相关联,失控性因子分与额叶病变(B=-3.609,P=0.023)相关联,戒断性因子分与丘脑病变(B=-5.047,P=0.007)、额叶病变(B=-2.204,P=0.024)相关联,逃避性因子分与顶叶病变(B=-1.867,P=0.032)相关联,低效性因子分与壳核病变(B=-1.789,P=0.016)、额叶病变(B=-1.592,P=0.044)相关联。结论脑型WD患者较肝型有更高的数字成瘾倾向,数字成瘾倾向与冲动性相关。WD患者的数字成瘾倾向可能与壳核、丘脑、额叶等多个脑区病变引起的冲动控制障碍有关。展开更多
Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by alteration of the adenosine triphosphatase 7B gene. It is rare to diagnose WD below the age of three years. Molecular genetic testin...Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by alteration of the adenosine triphosphatase 7B gene. It is rare to diagnose WD below the age of three years. Molecular genetic testing is one of the most important diagnostic methods and may confirm the diagnosis in equivocal cases. We report a case of a 9-mo old boy with WD who presented as chronic hepatitis. Genetic analysis showed compound heterozygotes of p.G1186S and c.4006delA.展开更多
AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mea...AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene(mutation): ATP7B(H1069Q), HFE(C282Y, H63D),UGT1A1(TA)7, and SERPINA1(PiZ)] were detected by polymerase chain reaction(PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61(76%), 7(9%), and 12(15%) patients, respectively. Among all 86 patients, 50(58%) reached an early viral response and 70(81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls(patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The(TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels(beta regression coefficient =-295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.展开更多
Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency an...Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease.Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia,Wilson's disease,deficiencies of divalent ions,or malnutrition.Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis,the use of certain medications,and in bone disease.Finally,subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia.The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.展开更多
文摘BACKGROUND： ATP7B gene exon 8 Arg778Leu and exon 12 Arg952Lys are gene mutation hot spots in Chinese Han patients with hepatolenticular degeneration, or Wilson＇s disease （WD）. However, the gene fragments are too short for detection and the mutation detection rate remains low. OBJECTIVE： To analyze DNA sequences of ATP7B gene exon 8-exon 9 and exon 10-exon 12 sections. DESIGN, TIME AND SE＇I-rlNG： A concurrent, non-randomized, controlled, genetic polymorphism study was performed at the Anhui Medical Genetics Center, Anhui, China from March to July in 2009. PARTICIPANTS： Fifty patients, who were admitted to the Department of Neurology at the First Affiliated Hospital of Anhui Traditional Chinese Medical College between March and July in 2009, were diagnosed with WD. The WD group comprised 32 males and 18 females, with an average age of （18.8 ± 8.3） years. WD was confirmed by clinical observation, as well as physical, imaging, and biochemical examinations, including testing for serum copper, ceruloplasmin, and copper oxidase. The control group comprised 20 normal subjects, who underwent physical examination at the First Affiliated Hospital of Anhui Traditional Chinese Medical College, and included 13 males and 7 females, with an average age of （27.9 ± 2.4） years. All subjects were Chinese Han population. METHODS： Genomic DNA was extracted from 50 WD patients and 20 normal controls. Polymerase chain reaction amplification of ATP7B gene exon 8-exon 9 （about 1 100 bp） and exon 10-exon 12 （about 850 bp） segments was performed. DNA exon-intron amplification products from all subjects were processed through direct bidirectional sequencing, and sequencing results were analyzed. MAIN OUTCOME MEASURES： Sequence changes of ATPTB gene exon 8-exon 9 and exon 10-exon 12 segments. RESULTS： In the 50 included WD patients, ATP7B gene intron 8 nt53592A → G with nt53671G→ A homozygous mutation was detected between exon 8-exon 9 in seven cases; exon 8 Arg778Leu mutations with Leu770Leu synonymous mutation was detected in four cases; exert 11 Gly790Arg heterozygous missense mutation between exon 10-exon 12 was found in four cases; exon 12 Arg952Lys heterozygous missense mutation was seen in 11 cases; and two additional cases were associated with exon 1211e929Val polymorphism. CONCLUSION： ATP7B gene intron 8 mutation is a possible pathogenic mutation that is associated with WD pathogenesis. The exon 11 mutation rate accounts for 8% of all WD patients, and the very few previously reported cases deserve further study.
文摘本文简要介绍第九届国际帕金森病暨运动障碍疾病研讨会及中国卒中学会移动医学上海论坛的学术内容。会议在2023年6月8日—10日在上海召开,世界神经病学争议大会会务组核心团队支持,由上海交通大学医学院附属第一人民医院及其嘉定分院主办。王晓平、Amos D Korczyn和赵钢教授担任大会主席,来自巴基斯坦、以色列、美国、希腊和瑞典等国家近10位知名专家通过Zoom视频软件进行会议演讲,就帕金森病、脑血管病、癫痫、偏头痛、肝豆状核变性等罕见病进行了广泛的学术交流,并展开了类似世界神经病学争议大会的热烈讨论和辩论,邀请了多位专业的双语(英语⁃中文)同步翻译,取得了很好的交流效果,吸引了国际上超过30000人次以上的观众和听众来收看和收听。
文摘目的探讨Wilson病(Wilson disease,WD)患者冲动性对数字成瘾倾向的影响及其相关因素。方法纳入66例WD患者为研究对象,根据临床表现分为脑型组42例、肝型组24例。采用网络成瘾量表(internet addiction test,IAT)评估患者网络成瘾倾向,总分>50分界定为具有网络成瘾倾向;使用Barratt冲动量表中文版(the Chinese version of the Barratt impulsiveness scale,11version,BIS-11-C)评估患者冲动性;手机依赖量表(mobile phone addiction index,MPAI)评估对手机使用的依赖程度;通过颅脑MRI检查患者病变脑区的部位和累计频次。结果66例WD患者中有数字成瘾倾向者45例(68.2%),其中脑型组中35例(53.0%)、肝型组中10例(15.2%),两组成瘾倾向者比例差异有统计学意义(P=0.001)。脑型组患者在BIS-11-C、MPAI量表多项因子分上高于肝型组(P<0.05)。所有患者MPAI量表中失控性因子分与BIS-11-C量表中的注意力冲动性因子分(r=0.499,P=0.001)、运动冲动性因子分(r=0.553,P=0.001)、无计划冲动性因子分(r=0.535,P=0.001)、冲动控制总分(r=0.653,P=0.001)正相关。线性回归分析显示注意力冲动性因子分与额叶病变(B=-1.634,P=0.018)相关联,失控性因子分与额叶病变(B=-3.609,P=0.023)相关联,戒断性因子分与丘脑病变(B=-5.047,P=0.007)、额叶病变(B=-2.204,P=0.024)相关联,逃避性因子分与顶叶病变(B=-1.867,P=0.032)相关联,低效性因子分与壳核病变(B=-1.789,P=0.016)、额叶病变(B=-1.592,P=0.044)相关联。结论脑型WD患者较肝型有更高的数字成瘾倾向,数字成瘾倾向与冲动性相关。WD患者的数字成瘾倾向可能与壳核、丘脑、额叶等多个脑区病变引起的冲动控制障碍有关。
文摘Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by alteration of the adenosine triphosphatase 7B gene. It is rare to diagnose WD below the age of three years. Molecular genetic testing is one of the most important diagnostic methods and may confirm the diagnosis in equivocal cases. We report a case of a 9-mo old boy with WD who presented as chronic hepatitis. Genetic analysis showed compound heterozygotes of p.G1186S and c.4006delA.
基金Supported by The Latvian Council of Science,National Project,Nos.09.1384 and 10.0010.02
文摘AIM:To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. METHODS:This study included 86 patients with chronic hepatitis C(55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene(mutation): ATP7B(H1069Q), HFE(C282Y, H63D),UGT1A1(TA)7, and SERPINA1(PiZ)] were detected by polymerase chain reaction(PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. RESULTS: The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61(76%), 7(9%), and 12(15%) patients, respectively. Among all 86 patients, 50(58%) reached an early viral response and 70(81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Casecontrol analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls(patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The(TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels(beta regression coefficient =-295.7, P = 0.0087). CONCLUSION: Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.
文摘Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease.Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia,Wilson's disease,deficiencies of divalent ions,or malnutrition.Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis,the use of certain medications,and in bone disease.Finally,subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia.The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.
