Intra-mitochondrial Methylation Deficiency Due to Mutations in SLC25A26.

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

Am. J. Hum. Genet. 97 (5) 761-768 [2015-11-05; online 2015-11-03]

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.

Clinical Genomics Stockholm

NGI Stockholm (Genomics Applications)

NGI Stockholm (Genomics Production)

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PubMed 26522469

DOI 10.1016/j.ajhg.2015.09.013

Crossref 10.1016/j.ajhg.2015.09.013

S0002-9297(15)00402-4

pmc PMC4667130