Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy.
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.
Bortot
B
B
Child Neurology and Psychiatry Unit, Institute of Child Health IRCCS, Burlo Garofolo, Via dell'Istria 65/1, 34137 Trieste, Italy.
Barbi
E
E
Biffi
S
S
Angelini
C
C
Faleschini
E
E
Severini
G M
GM
Carrozzi
M
M
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*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012358:RNA, Transfer, Met; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3