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
Background： Spinocerebellar ata^ias （SCAs） are a group ofneurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radio...Background： Spinocerebellar ata^ias （SCAs） are a group ofneurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs. Methods： In this study, we investigated 10 SCAs Chinese families with SCAI, SCA3/Machado-Joseph disease （MJD}, SCA7, SCAB. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but tailed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were perlbrmed. Results： We found that SCA3/MJD was the most common subtype in Hart population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively con＇elated with the number of cytosine-adenine-guanine （CAG） repeats： the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset. Conchlsions： Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.展开更多
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.
文摘Background： Spinocerebellar ata^ias （SCAs） are a group ofneurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs. Methods： In this study, we investigated 10 SCAs Chinese families with SCAI, SCA3/Machado-Joseph disease （MJD}, SCA7, SCAB. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but tailed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were perlbrmed. Results： We found that SCA3/MJD was the most common subtype in Hart population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively con＇elated with the number of cytosine-adenine-guanine （CAG） repeats： the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset. Conchlsions： Collectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.
