The mitochondrial DNA variant m.9032T C in MT-ATP6 encoding p.(Leu169Pro) causes a complex mitochondrial neurological syndrome
| Autor: | Ting Chen, Austin Larson, Marisa W. Friederich, David M. Mirsky, Johan L.K. Van Hove, Lee-Jun C. Wong, Emily Shelkowitz, Kaz M. Knight, Yue Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Microcephaly Mitochondrial DNA Ataxia Mitochondrial Diseases Biology Polymorphism Single Nucleotide Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Humans Child Molecular Biology Brain High-Throughput Nucleotide Sequencing Cell Biology Sequence Analysis DNA Mitochondrial Proton-Translocating ATPases medicine.disease Molecular biology Phenotype 030104 developmental biology Mitochondrial biogenesis Amino Acid Substitution Lactic acidosis MT-ATP6 biology.protein Molecular Medicine medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Mitochondrion |
| ISSN: | 1872-8278 |
| Popis: | Diagnosing complex V deficiencies caused by new variants in mitochondrial DNA is challenging due to the rarity, phenotypic diversity, and limited functional assessments. We describe a child with the m.9032T > C variant in MT-ATP6 encoding p.(Leu169Pro), with primary presentation of microcephaly, ataxia, hearing loss, and lactic acidosis. Functional studies reveal abnormal fragment F1 of complex V on blue native gel electrophoresis. Respirometry showed excessively tight coupling through complex V depressing oxygen consumption upon ADP stimulation and an excessive increase following uncoupling, in the presence of upregulation of mitochondrial biogenesis. These data add evidence about pathogenicity and functional impact of this variant. |
| Databáze: | OpenAIRE |
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