Chapter title |
Muscle Weakness, Cardiomyopathy, and L-2-Hydroxyglutaric Aciduria Associated with a Novel Recessive SLC25A4 Mutation
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Chapter number | 93 |
Book title |
JIMD Reports, Volume 43
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Published in |
JIMD Reports, January 2018
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DOI | 10.1007/8904_2018_93 |
Pubmed ID | |
Book ISBNs |
978-3-66-258613-6, 978-3-66-258614-3
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Authors |
Anja von Renesse, Susanne Morales-Gonzalez, Esther Gill, Gajja S. Salomons, Werner Stenzel, Markus Schuelke, von Renesse, Anja, Morales-Gonzalez, Susanne, Gill, Esther, Salomons, Gajja S., Stenzel, Werner, Schuelke, Markus |
Abstract |
Mutations in SLC25A4 (syn. ANT1, Adenine nucleotide translocase, type 1) are known to cause either autosomal dominant progressive external ophthalmoplegia (adPEO) or recessive mitochondrial myopathy, hypertrophic cardiomyopathy, and lactic acidosis. Whole exome sequencing in a young man with myopathy, subsarcolemmal mitochondrial aggregations, cardiomyopathy, lactic acidosis, and L-2-hydroxyglutaric aciduria (L-2-HGA) revealed a new homozygous mutation in SLC25A4 [c.653A>C, NM_001151], leading to the replacement of a highly conserved glutamine by proline [p.(Q218P); NP_001142] that most likely affects the folding of the ANT1 protein. No pathogenic mutation was found in L2HGDH, which is associated with "classic" L-2-HGA. Furthermore, L-2-HGDH enzymatic activity in the patient fibroblasts was normal. Long-range PCR and Southern blot confirmed absence of mtDNA-deletions in blood and muscle. The disturbed ADP/ATP transport across the inner mitochondrial membrane may lead to an accumulation of different TCA-cycle intermediates such as 2-ketoglutarate (2-KG) in our patient. As L-2-HG is generated from 2-KG we hypothesize that the L-2-HG increase is a secondary effect of 2-KG accumulation. Hence, our report expands the spectrum of laboratory findings in ANT1-related diseases and hints towards a connection with organic acidurias. |
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United States | 1 | 50% |
Unknown | 1 | 50% |
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Members of the public | 2 | 100% |
Mendeley readers
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Unknown | 13 | 100% |
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Student > Ph. D. Student | 4 | 31% |
Professor | 1 | 8% |
Unspecified | 1 | 8% |
Student > Doctoral Student | 1 | 8% |
Student > Master | 1 | 8% |
Other | 0 | 0% |
Unknown | 5 | 38% |
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Biochemistry, Genetics and Molecular Biology | 1 | 8% |
Unspecified | 1 | 8% |
Social Sciences | 1 | 8% |
Immunology and Microbiology | 1 | 8% |
Other | 0 | 0% |
Unknown | 6 | 46% |