title: Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy.
abstract: We report a 12-year-old patient with growth retardation, exercise intolerance, lactic acidosis (increasing after exercise) and autoimmune polyendocrinopathy type 2. Muscle biopsy shows abundant COX-negative fibers, subsarcolemmal mitochondrial aggregates and markedly reduced activities of all respiratory chain complexes. Genetic analysis identified two new cosegregating mutations in Met-tRNA (m.4415A>G) and Cox III (m.9922A>C), located in highly conserved regions of MtDNA. Both the mutations are heteroplasmics in multiple patients' tissues. Single-muscle fiber analysis showed significantly higher levels of both the mutations in COX-negative than in normal fibers. In addition, a possible link between the mitochondrial dysfunction and the autoimmune disease is suggested.
authors.affiliation: Child Neurology and Psychiatry Unit, Institute of Child Health IRCCS, Burlo Garofolo, Via dell'Istria 65/1, 34137 Trieste, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Bortot
authors.forename: E
authors.initials: E
authors.lastname: Barbi
authors.forename: S
authors.initials: S
authors.lastname: Biffi
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: E
authors.initials: E
authors.lastname: Faleschini
authors.forename: G M
authors.initials: GM
authors.lastname: Severini
authors.forename: M
authors.initials: M
authors.lastname: Carrozzi
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics*; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D017354:Point Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012358:RNA, Transfer, Met / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012358:RNA, Transfer, Met; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3