De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome
Background. The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochond...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/5184647 |
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| author | Zhixin Jiang Yinan Zhang Jingbin Yan Fengwen Li Xinqian Geng Huijuan Lu Xiaoer Wei Yanmei Feng Congrong Wang Weiping Jia |
| author_facet | Zhixin Jiang Yinan Zhang Jingbin Yan Fengwen Li Xinqian Geng Huijuan Lu Xiaoer Wei Yanmei Feng Congrong Wang Weiping Jia |
| author_sort | Zhixin Jiang |
| collection | DOAJ |
| description | Background. The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochondrial DNA mutations related to atypical clinical phenotypes. Methods. Heteroplasmy levels of the m.3243A>G mutation in peripheral blood, saliva, and urine sediment of 31 individuals from 10 unrelated pedigrees were measured by pyrosequencing. Clinical evaluations including endocrinological, audiological, and magnetic resonance imaging (MRI) examinations, mitochondrial function evaluation in peripheral blood mononuclear cells (PBMCs), and whole mitochondrial DNA (mtDNA) sequencing were performed among the spontaneous mutant pedigrees. Results. Among the 10 unrelated MIDD pedigrees, we found that the de novo m.3243A>G mutation occurred in the family 1957 (F1957). The proband (F1957-II-1) and her son (F1957-III-1) both manifested diabetes with mild bilateral sensorineural hearing loss (SNHL) and abnormal brain MRI, and F1957-III-1 also complained of severe nausea and vomiting. Mitochondrial function evaluation in PBMCs revealed an increased level of ROS generation and decreased levels of ATP and mitochondrial membrane potential (ΔΨm) in the two m.3243A>G carriers. Whole mtDNA sequencing also revealed a de novo heteroplasmic substitution at m.16093T>C in both the proband and her son. Conclusions. Our study showed that de novo m.3243A>G mutation accompanied by other point mutations may occur in the very early embryonic or germ cell stage without maternal inheritance, bringing about both typical and atypical clinical features. |
| format | Article |
| id | doaj-art-ea4338c0c94240a49af88fd3a03e9ff8 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ea4338c0c94240a49af88fd3a03e9ff82025-02-03T01:31:44ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/51846475184647De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD SyndromeZhixin Jiang0Yinan Zhang1Jingbin Yan2Fengwen Li3Xinqian Geng4Huijuan Lu5Xiaoer Wei6Yanmei Feng7Congrong Wang8Weiping Jia9Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, The Metabolic Diseases Biobank, Center for Translational Medicine, Shanghai Key Laboratory of Diabetes, Shanghai 200233, ChinaShanghai Institute of Medical Genetics, Shanghai Children’s Hospital, Shanghai Jiao Tong University, The Key Laboratory of Embryo Molecular Biology, Ministry of Health of China & Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Department of Diagnostic Radiology, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Department of Otolaryngology Head and Neck Surgery, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Department of Endocrinology and Metabolism, Shanghai 200233, ChinaBackground. The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochondrial DNA mutations related to atypical clinical phenotypes. Methods. Heteroplasmy levels of the m.3243A>G mutation in peripheral blood, saliva, and urine sediment of 31 individuals from 10 unrelated pedigrees were measured by pyrosequencing. Clinical evaluations including endocrinological, audiological, and magnetic resonance imaging (MRI) examinations, mitochondrial function evaluation in peripheral blood mononuclear cells (PBMCs), and whole mitochondrial DNA (mtDNA) sequencing were performed among the spontaneous mutant pedigrees. Results. Among the 10 unrelated MIDD pedigrees, we found that the de novo m.3243A>G mutation occurred in the family 1957 (F1957). The proband (F1957-II-1) and her son (F1957-III-1) both manifested diabetes with mild bilateral sensorineural hearing loss (SNHL) and abnormal brain MRI, and F1957-III-1 also complained of severe nausea and vomiting. Mitochondrial function evaluation in PBMCs revealed an increased level of ROS generation and decreased levels of ATP and mitochondrial membrane potential (ΔΨm) in the two m.3243A>G carriers. Whole mtDNA sequencing also revealed a de novo heteroplasmic substitution at m.16093T>C in both the proband and her son. Conclusions. Our study showed that de novo m.3243A>G mutation accompanied by other point mutations may occur in the very early embryonic or germ cell stage without maternal inheritance, bringing about both typical and atypical clinical features.http://dx.doi.org/10.1155/2019/5184647 |
| spellingShingle | Zhixin Jiang Yinan Zhang Jingbin Yan Fengwen Li Xinqian Geng Huijuan Lu Xiaoer Wei Yanmei Feng Congrong Wang Weiping Jia De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome Journal of Diabetes Research |
| title | De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome |
| title_full | De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome |
| title_fullStr | De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome |
| title_full_unstemmed | De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome |
| title_short | De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome |
| title_sort | de novo mutation of m 3243a g together with m 16093t c associated with atypical clinical features in a pedigree with midd syndrome |
| url | http://dx.doi.org/10.1155/2019/5184647 |
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