2021年1月4日,《核酸研究》(Nucleic Acids Research)在线发表了管敏鑫教授团队有关线粒体tRNA反密码子环37位修饰缺陷导致母系遗传性耳聋的最新研究成果“A deafness-associated tRNA mutation caused pleiotropic effects on the m1G3...2021年1月4日,《核酸研究》(Nucleic Acids Research)在线发表了管敏鑫教授团队有关线粒体tRNA反密码子环37位修饰缺陷导致母系遗传性耳聋的最新研究成果“A deafness-associated tRNA mutation caused pleiotropic effects on the m1G37 modification,processing,stability and aminoacylation of tRNAIle and mitochondrial translation”(https://doi.org/10.1093/nar/gkaa1225)。该研究对核酸修饰异常引发的线粒体tRNA结构和功能变化导致听力损伤的机制提出了新的见解,为耳聋的致病机制研究提供了新的视角。展开更多
Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Metho...Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^(Leu(UUR)) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P=0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^(Leu(UUR)) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^(Leu(UUR)) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.展开更多
文摘2021年1月4日,《核酸研究》(Nucleic Acids Research)在线发表了管敏鑫教授团队有关线粒体tRNA反密码子环37位修饰缺陷导致母系遗传性耳聋的最新研究成果“A deafness-associated tRNA mutation caused pleiotropic effects on the m1G37 modification,processing,stability and aminoacylation of tRNAIle and mitochondrial translation”(https://doi.org/10.1093/nar/gkaa1225)。该研究对核酸修饰异常引发的线粒体tRNA结构和功能变化导致听力损伤的机制提出了新的见解,为耳聋的致病机制研究提供了新的视角。
文摘Objective To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features. Methods Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations. Results Family members on the maternal side all harbored the tRNA^(Leu(UUR)) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P=0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found. Conclusions The main cause of diabetes in this pedigree is the tRNA^(Leu(UUR)) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNA^(Leu(UUR)) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.
