PUBLICATION
Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans
- Authors
- Shamseldin, H.E., Smith, L.L., Kentab, A., Alkhalidi, H., Summers, B., Alsedairy, H., Xiong, Y., Gupta, V.A., Alkuraya, F.S.
- ID
- ZDB-PUB-151107-3
- Date
- 2016
- Source
- Human genetics 135(1): 21-30 (Journal)
- Registered Authors
- Gupta, Vandana A
- Keywords
- none
- MeSH Terms
-
- Adenine Nucleotide Translocator 1/genetics*
- Adolescent
- Animals
- Female
- Humans
- Male
- Mitochondrial Myopathies/genetics*
- Models, Animal
- Mutation*
- Pedigree
- RNA, Messenger/genetics
- Zebrafish
- PubMed
- 26541337 Full text @ Hum. Genet.
Citation
Shamseldin, H.E., Smith, L.L., Kentab, A., Alkhalidi, H., Summers, B., Alsedairy, H., Xiong, Y., Gupta, V.A., Alkuraya, F.S. (2016) Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans. Human genetics. 135(1):21-30.
Abstract
Myopathies are heterogeneous disorders characterized clinically by weakness and hypotonia, usually in the absence of gross dystrophic changes. Mitochondrial dysfunction is a frequent cause of myopathy. We report a simplex case born to consanguineous parents who presented with muscle weakness, lactic acidosis, and muscle changes suggestive of mitochondrial dysfunction. Combined autozygome and exome analysis revealed a missense variant in the SLC25A42 gene, which encodes an inner mitochondrial membrane protein that imports coenzyme A into the mitochondrial matrix. Zebrafish slc25a42 knockdown morphants display severe muscle disorganization and weakness. Importantly, these features are rescued by normal human SLC25A42 RNA, but not by RNA harboring the patient's variant. Our data support a potentially causal link between SLC25A42 mutation and mitochondrial myopathy in humans.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping