The polymorphic CAG repeats in the IT15 gene in Chinese normal and Huntington’s dis-ease(HD)chromosomes were determined by using nested PCR and denaturing polyacry-lamide gel electrophoretic autoradiography as well a...The polymorphic CAG repeats in the IT15 gene in Chinese normal and Huntington’s dis-ease(HD)chromosomes were determined by using nested PCR and denaturing polyacry-lamide gel electrophoretic autoradiography as well as direct sequencing analysis.A total of40 normal individuals and 122 members of 13 unrelated HD families originating from Shang-hai,Jiangsu,Zhejiang,Anhui,Shandong,Guangdong and Henan,respectively,were in-volved in this study.The results showed that the(CAG)n repeat numbers in 270 normal al-leles ranged from 13 to 26 but most in 16;while in 54 HD alleles,the CAG repeats from 40to 94,with an unstable inheritance of expanded repeats in some families.There was no over-lap between the normal and affected alleles.Additionally,the presymptomatic diagnosis in103 family members at risk for HD disclosed that 35 individuals had HD alleles,which were-in accordance with the pedigree analysis and clinical investigation.All these results indicatedthat the dynamic mutation in IT15 gene was responsible for the genetic defect in the ChineseHD patients and that a correlation existed between the numbers of(CAG)n repeat and theonset age of the disease.All-of these provide valuable data for HD molecular diagnosis,ge-netic counselling and genetic health.展开更多
Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathog...Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele： Ⅲ10 Ⅲ12, IIIt4, Ⅳ3, and Ⅴ2 carded （CAG） 48, Ⅳ11 and Ⅳ12 carried （CAG） 67, and Ⅳ14 carried （CAG） 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation （characterized by earlier age of onset and increasing severity） of the patientⅣ12.展开更多
We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington＇s disease. Among 17 family members across three generations, four patients （Ⅱ2, Ⅱ6, Ⅲ5, and Ⅲ9） show typ...We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington＇s disease. Among 17 family members across three generations, four patients （Ⅱ2, Ⅱ6, Ⅲ5, and Ⅲ9） show typical Huntington＇s disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members （Ⅱ2, Ⅱ6, and Ⅲ5）. Moreover, genetic analysis identified abnormally amplified CAG sequence repeats （〉 40） in two members （Ⅲ5 and Ⅲ9）. Among borderline cases, with clinical symptoms and brain imaging features of Huntington＇s disease, two cases were identified （Ⅱ2 and Ⅱ6）, but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington＇s disease. Our findings suggest that clinical diagnosis of Huntington＇s disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.展开更多
基金the High Technology Research Development Programme of China
文摘The polymorphic CAG repeats in the IT15 gene in Chinese normal and Huntington’s dis-ease(HD)chromosomes were determined by using nested PCR and denaturing polyacry-lamide gel electrophoretic autoradiography as well as direct sequencing analysis.A total of40 normal individuals and 122 members of 13 unrelated HD families originating from Shang-hai,Jiangsu,Zhejiang,Anhui,Shandong,Guangdong and Henan,respectively,were in-volved in this study.The results showed that the(CAG)n repeat numbers in 270 normal al-leles ranged from 13 to 26 but most in 16;while in 54 HD alleles,the CAG repeats from 40to 94,with an unstable inheritance of expanded repeats in some families.There was no over-lap between the normal and affected alleles.Additionally,the presymptomatic diagnosis in103 family members at risk for HD disclosed that 35 individuals had HD alleles,which were-in accordance with the pedigree analysis and clinical investigation.All these results indicatedthat the dynamic mutation in IT15 gene was responsible for the genetic defect in the ChineseHD patients and that a correlation existed between the numbers of(CAG)n repeat and theonset age of the disease.All-of these provide valuable data for HD molecular diagnosis,ge-netic counselling and genetic health.
文摘Objective To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease （HD） family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. Methods According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. Results Eight of twenty-five family members carried abnormal allele： Ⅲ10 Ⅲ12, IIIt4, Ⅳ3, and Ⅴ2 carded （CAG） 48, Ⅳ11 and Ⅳ12 carried （CAG） 67, and Ⅳ14 carried （CAG） 63, in contrast with the 8-25 CAG trinucleotides in the members of control group. Ⅳ14 carried 15 more CAG trinucleotides than her father Ⅲ10. Conclusion The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation （characterized by earlier age of onset and increasing severity） of the patientⅣ12.
基金supported by the Fundamental Research Funds for the Central Universities,No.20100141110017,20103030201000217 and 201130302020008
文摘We report brain imaging and genetic diagnosis in a family from Wuhan, China, with a history of Huntington＇s disease. Among 17 family members across three generations, four patients （Ⅱ2, Ⅱ6, Ⅲ5, and Ⅲ9） show typical Huntington＇s disease, involuntary dance-like movements. Magnetic resonance imaging found lateral ventricular atrophy in three members （Ⅱ2, Ⅱ6, and Ⅲ5）. Moreover, genetic analysis identified abnormally amplified CAG sequence repeats （〉 40） in two members （Ⅲ5 and Ⅲ9）. Among borderline cases, with clinical symptoms and brain imaging features of Huntington＇s disease, two cases were identified （Ⅱ2 and Ⅱ6）, but shown by mutation analysis for CAG expansions in the important transcript 15 gene, to be non-Huntington＇s disease. Our findings suggest that clinical diagnosis of Huntington＇s disease requires a combination of clinical symptoms, radiological changes, and genetic diagnosis.
