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A novel ISCA2 variant responsible for an early-onset neurodegenerative mitochondrial disorder: a case report of multiple mitochondrial dysfunctions syndrome 4.

ABSTRACT: BACKGROUND:Multiple Mitochondrial Dysfunctions Syndrome 4 (MMDS4) is manifested as a result of ISCA2 mutations. ISCA2 is a vital component of 4Fe-4S clusters assembly machine. Therefore, in MMDS4 patients, deficient mitochondrial respiratory chain complexes I and II, Aconitase and Succinate dehydrogenase of Kerbs cycle and Lipoic Acid Synthetase in the biosynthesis of lipoic acid are expected. CASE PRESENTATIONS:A 7?months boy in an Iranian consanguineous family with progressive neurodegenerative problems was referred to us. Primarily, general laboratory tests, Abdomen ultrasonography and brain magnetic resonance imaging were performed. In order to find out the genetic problem in this case Whole Exome Sequencing (WES) following by Sanger sequencing was carried out. A novel variant (c.355G?>?A, p.Ala119Thr) in ISCA2 gene was identified by WES in the proband. Confirmation and segregation in the family for this variant was performed by Sanger sequencing. In-Silico prediction of the ISCA2 secondary structure showed that a helix motif in the Fe-S biosynthesis domain of ISCA2 protein will be eliminated as a result of this variant. CONCLUSIONS:We reported the first patient with ISCA2 variant in Iranian population and the third one in the world reported for ISCA2 gene, so far associated with early-onset mitochondrial neurodegeneration. However further functional studies on this variant or finding it in other patients with similar clinical problems are needed to confirm the pathogenicity of this variant.

SUBMITTER: Eidi M

PROVIDER: S-EPMC6612116 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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A novel ISCA2 variant responsible for an early-onset neurodegenerative mitochondrial disorder: a case report of multiple mitochondrial dysfunctions syndrome 4.

Eidi Milad M Garshasbi Masoud M

BMC neurology 20190706 1

<h4>Background</h4>Multiple Mitochondrial Dysfunctions Syndrome 4 (MMDS4) is manifested as a result of ISCA2 mutations. ISCA2 is a vital component of 4Fe-4S clusters assembly machine. Therefore, in MMDS4 patients, deficient mitochondrial respiratory chain complexes I and II, Aconitase and Succinate dehydrogenase of Kerbs cycle and Lipoic Acid Synthetase in the biosynthesis of lipoic acid are expected.<h4>Case presentations</h4>A 7 months boy in an Iranian consanguineous family with progressive n ...[more]

PMID: 31279336

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Project description:Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes, the mitochondria are required for multiple pivotal processes that include the production of biological energy, the biosynthesis of reactive oxygen species, the control of calcium homeostasis, and the triggering of cell death. The disruption of anyone of these processes has been shown to impact strongly the function of all cells, but especially of neurons. In this review, we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis, Parkinson's disease and Alzheimer's disease. We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle: fusion, fission, production of reactive oxygen species and energy failure. Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes. Therefore, in order to get in depth insights into their health status in neurodegenerative diseases, we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes. Current techniques include Mitostress, Mitotracker, transmission electron microscopy, oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health. We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction. These include canonical drugs, natural compounds, supplements, lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy. In conclusion, because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases, it is critical to develop novel methods to measure the mitochondrial state, and novel therapeutic strategies aimed at improving their health.

Dataset Information

A novel ISCA2 variant responsible for an early-onset neurodegenerative mitochondrial disorder: a case report of multiple mitochondrial dysfunctions syndrome 4.

Publications

A novel ISCA2 variant responsible for an early-onset neurodegenerative mitochondrial disorder: a case report of multiple mitochondrial dysfunctions syndrome 4.

Similar Datasets

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