학술논문
Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy
Document Type
Article
Source
Subject
*TRANSFER RNA
*GENETIC mutation
*AUTOIMMUNE diseases
*ENDOCRINE diseases
*BIOPSY
*MITOCHONDRIAL DNA
*FIBERS
*PATIENTS
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Language
ISSN
1567-7249
Abstract
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. [Copyright &y& Elsevier]