RRC ID 35107
Author Kishita Y, Pajak A, Bolar NA, Marobbio CM, Maffezzini C, Miniero DV, Monné M, Kohda M, Stranneheim H, Murayama K, Naess K, Lesko N, Bruhn H, Mourier A, Wibom R, Nennesmo I, Jespers A, Govaert P, Ohtake A, Van Laer L, Loeys BL, Freyer C, Palmieri F, Wredenberg A, Okazaki Y, Wedell A.
Title Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26.
Journal Am J Hum Genet
Abstract S-adenosylmethionine (SAM) is the predominant methyl group donor and has a large spectrum of target substrates. As such, it is essential for nearly all biological methylation reactions. SAM is synthesized by methionine adenosyltransferase from methionine and ATP in the cytoplasm and subsequently distributed throughout the different cellular compartments, including mitochondria, where methylation is mostly required for nucleic-acid modifications and respiratory-chain function. We report a syndrome in three families affected by reduced intra-mitochondrial methylation caused by recessive mutations in the gene encoding the only known mitochondrial SAM transporter, SLC25A26. Clinical findings ranged from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness. We show that SLC25A26 mutations cause various mitochondrial defects, including those affecting RNA stability, protein modification, mitochondrial translation, and the biosynthesis of CoQ10 and lipoic acid.
Volume 97(5)
Pages 761-8
Published 2015-11-5
DOI 10.1016/j.ajhg.2015.09.013
PII S0002-9297(15)00402-4
PMID 26522469
PMC PMC4667130
MeSH Amino Acid Sequence Amino Acid Transport Systems / genetics* Calcium-Binding Proteins / genetics* Child, Preschool DNA Methylation* Female Humans Male Mitochondrial Diseases / genetics* Mitochondrial Diseases / pathology* Molecular Sequence Data Muscle Weakness / genetics* Muscle Weakness / pathology Mutation / genetics* Pedigree Prognosis RNA Stability S-Adenosylmethionine / metabolism* Sequence Homology, Amino Acid Thioctic Acid / metabolism Ubiquinone / analogs & derivatives Ubiquinone / metabolism
IF 10.502
Times Cited 22
DNA material CS-CA-MCS (RDB05963)