The mitochondrial DNA mutation @entity19229 predisposes to @entity393 following @entity4028 antibiotic exposure in an idiosyncratic dose-independent manner. However, it may also cause maternally @entity393 in the absence of @entity4028 exposure or any other clinical features ( @entity3491 ). Although @entity19229 was identified as a cause of @entity2319 more than twenty years ago, the pathogenic mechanism of this mutation of ribosomal RNA remains controversial. Different mechanistic concepts have been proposed. Most recently, evidence from cell lines and animal models suggested that @entity1 with @entity19229 may have more 12S rRNA N6, @entity68315 (m(6) 2A) methylation than controls, so-called 'hypermethylation'. This has been implicated as a pathogenic mechanism of mitochondrial dysfunction but has yet to be validated in @entity1 . 12S m(6) 2A rRNA methylation, by the @entity5909 ( @entity29993 ) enzyme, occurs at two successive @entity2036 (m.1584A and m.1583A) in close proximity to @entity19229 . We examined m(6) 2A methylation in 14 @entity1 with @entity19229 , and controls, and found all detectable 12S rRNA transcripts to be methylated in both groups. Moreover, different RNA samples derived from the same @entity1 (lymphocyte, fibroblast and lymphoblast) revealed that only transformed cells contained some unmethylated 12S rRNA transcripts, with all detectable 12S rRNA transcripts derived from primary samples m(6) 2A-methylated. Our data indicate that @entity29993 12S m(6) 2A rRNA hypermethylation is unlikely to be a pathogenic mechanism and may be an artefact of previous experimental models studied. We propose that RNA methylation studies in experimental models should be validated in primary clinical samples to ensure that they are applicable to the @entity1 situation.

Mitochondrial m.1584A 12S m62A rRNA methylation in families with XXXX associated @entity393 .

@entity19229 :: ('m|SUB|A|1555|G', 'DNAMutation') :: ['m.1555A>G'] @entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient'] @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides'] @entity3491 :: ('MESH:C580334', 'Disease') :: ['non-syndromic hearing loss'] @entity2319 :: ('MESH:D003638', 'Disease') :: ['deafness'] @entity29993 :: ('51106', 'Gene') :: ['TFB1M'] @entity393 :: ('MESH:D034381', 'Disease') :: ['inherited hearing loss', 'hearing loss'] @entity68315 :: ('CHEBI:28284', 'Chemical') :: ['N6-dimethyladenosine'] @entity4028 :: ('CHEBI:47779', 'Chemical') :: ['aminoglycoside'] @entity5909 :: ('7019', 'Gene') :: ['mitochondrial transcription factor 1']
@entity19229 :: (m|SUB|A|1555|G,DNAMutation) :: ['m.1555A>G']
