This study reports a case of a 75-year-old female Machado-Joseph disease patient exhibiting unstable walking and inaccurate hand holding for 8 months, which progressively worsened. Physical examination on admission sh...This study reports a case of a 75-year-old female Machado-Joseph disease patient exhibiting unstable walking and inaccurate hand holding for 8 months, which progressively worsened. Physical examination on admission showed cerebellar ataxia and a history of hypertension. Crania MRI demonstrated cerebellar and brain stem atrophy. Gene analysis showed abnormal amplification of the CAG trinucleotide repeat in exon 10 of the ataxin-3 （ATXN3） gene, resulting in 70-81 CAG repeats in the patient, with a significant positive family history.展开更多
Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or...Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother.展开更多
Background: Cognitive function of Machado Joseph disease (MJD) patients has n ot been clarified. Objectives: To determine the characteristics of cognitive dys function in MJD patients and to assess the relationship of...Background: Cognitive function of Machado Joseph disease (MJD) patients has n ot been clarified. Objectives: To determine the characteristics of cognitive dys function in MJD patients and to assess the relationship of dysfunction to age at onset, age at examination, disease duration, education, ataxia, depression, anx iety, and CAG repeat length. Design: Case con trol study. Setting: Research o riented hospitals. Participants: Sixteen genetically confirmed MJD patients able to complete neuropsychological tests and 20 control subjects matched to patient s by age and education. Main Outcome Measures: Neuropsychological tests, includi ng general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety. Results: Machado Joseph disease patients scored sig nificantly lower than cont rols in verbal and visual memory, in visuospatial and constructional tasks, and in phonemic and semantic fluency tasks. None of these impairments correlated wit h CAG repeat length, age at onset, age at examination, disease duration, or educ ation. Verbal fluency (words named in a category) correlated with the Internatio nal Cooperative Ataxia Rating Scale score. Conclusion: Machado Joseph disease p atients have verbal and visual memory deficits, visuospatial and constructional dysfunction, and verbal fluency deficits, all unrelated to CAG repeat length.展开更多
Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene pr...Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 （CK2）. Methods The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase （GST） pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays. Results （1） Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. （2） In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. （3） CK2 phosphorylated wild type and expanded ataxin-3. Conclusion Ataxin-3 is a substrate of protein kinase CK2.展开更多
基金funded by Fengxian District Science Technology Commission Foundation of Shanghai,No.2010-101101,2011-110
文摘This study reports a case of a 75-year-old female Machado-Joseph disease patient exhibiting unstable walking and inaccurate hand holding for 8 months, which progressively worsened. Physical examination on admission showed cerebellar ataxia and a history of hypertension. Crania MRI demonstrated cerebellar and brain stem atrophy. Gene analysis showed abnormal amplification of the CAG trinucleotide repeat in exon 10 of the ataxin-3 （ATXN3） gene, resulting in 70-81 CAG repeats in the patient, with a significant positive family history.
基金grants from the National Science and Technology Pillar Program in the Eleventh Five-year Plan Period, No. 2006BAI05A07the Major State Basic Research Development Program of China (973 Program), No. 2006cb500700+5 种基金the National Key Technologies Research and Development Program of China, No. 2004BA720A03the National Natural Science Foundation of China, No. 30871354, 30710303061 and 30470619the Key Project in the Natural Science Foundation of Hunan Province, No. 08JJ3048the Natural Science Foundation of Hunan Province, No. 11JJ5071the Science and Technology Planning Project of Hunan Province, No. 2009SK3172the Graduate Degree Thesis Innovation Foundation of Central South University, No. 2008yb030
文摘Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother.
文摘Background: Cognitive function of Machado Joseph disease (MJD) patients has n ot been clarified. Objectives: To determine the characteristics of cognitive dys function in MJD patients and to assess the relationship of dysfunction to age at onset, age at examination, disease duration, education, ataxia, depression, anx iety, and CAG repeat length. Design: Case con trol study. Setting: Research o riented hospitals. Participants: Sixteen genetically confirmed MJD patients able to complete neuropsychological tests and 20 control subjects matched to patient s by age and education. Main Outcome Measures: Neuropsychological tests, includi ng general cognition, verbal and visual memory, working memory, visuospatial and constructional ability, language, executive function, depression, and anxiety. Results: Machado Joseph disease patients scored sig nificantly lower than cont rols in verbal and visual memory, in visuospatial and constructional tasks, and in phonemic and semantic fluency tasks. None of these impairments correlated wit h CAG repeat length, age at onset, age at examination, disease duration, or educ ation. Verbal fluency (words named in a category) correlated with the Internatio nal Cooperative Ataxia Rating Scale score. Conclusion: Machado Joseph disease p atients have verbal and visual memory deficits, visuospatial and constructional dysfunction, and verbal fluency deficits, all unrelated to CAG repeat length.
基金the National Natural Sciences Foundation of China (No. 30770664)a grant from Educational Committee of Anhui Province, China (No. ZD2008008-2).
文摘Objective Machado-Joseph disease （MJD）/Spinocerebellar ataxia type 3 （SCA3） is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 （CK2）. Methods The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase （GST） pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays. Results （1） Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. （2） In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. （3） CK2 phosphorylated wild type and expanded ataxin-3. Conclusion Ataxin-3 is a substrate of protein kinase CK2.
文摘脊髓小脑性共济失调(Spinocerebellar ataxia,SCA)是一组由小脑及其传入和传出连接变性引起的常染色体显性共济失调疾病,主要临床表现包括姿势和步态的异常、构音障碍、眼球运动障碍、视网膜病变、锥体外系及锥体束病变、周围神经损害等[1]。SCA属于罕见病,在欧洲不同地区进行的流行病学研究发现患病率为(0.9~3.0)/10万人[2]。根据临床表现或遗传学分类,迄今为止已经确立了40种SCA,其中包括SCA1-40。鉴定了28种SCA的致病基因[3],本文报道1例确诊为脊髓小脑性共济失调3型(Spinocerebellar ataxia type 3,SCA3)病例的临床表现、病史及相关文献报道如下。
