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MELAS syndrome associated with a tandem duplication in the D‐loop of mitochondrial DNA
Author(s) -
Li JY.,
Kong KW.,
Chang MH.,
Cheung SC.,
Lee HC.,
Pang CY.,
Wei YH.
Publication year - 1996
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1996.tb00025.x
Subject(s) - proband , melas syndrome , mitochondrial dna , gene duplication , tandem exon duplication , mitochondrial myopathy , lactic acidosis , genetics , point mutation , biology , mitochondrial encephalomyopathy , mutation , medicine , endocrinology , gene
We describe a family with two cases of adult‐onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) syndrome. Interestingly, the proband also had non‐insulin dependent diabetes mellitus and hyperthyroidism. Endocrinological studies demonstrated a high titer of TSH receptor antibody in the proband and elevated levels in her maternal relatives. Analysis of mitochondrial DNA (mtDNA) showed an A‐to‐G transition at nucleotide position 3243 in the tRNA Leu(UUR) gene (A3243G) in the three generations of the family. Furthermore, a previously described ~ 260 bp tandem duplication in the D‐loop region of mtDNA was also found in the proband and her maternal relatives. To our knowledge, such kind of duplication has never before been reported in the MELAS syndrome. The proportions of mtDNA with the ~260 bp tandem duplication and A3243G point mutation were 12.5% and 82% in the muscle, respectively, and 1.6% and 35% in the blood cells, respectively, of the proband. We conclude that the hyperthyroidism in this MELAS patient may be related to the tandem duplication in the D‐loop of mtDNA. This study further substantiates the importance of searching for additional genetic mutations in mitochondrial encephalomyopathic patients with new clinical phenotypes.