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MELAS‐ and kearns‐sayre‐type with myopathy and autoimmune polyendocrinopahy
Author(s) -
Ohno Kinji,
Yamamoto Masahiko,
Engel Andrew G.,
Michel C. Michel,
Roberts Lewis R.,
Tan Gerry H.,
Fatourechi Vahab
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410390612
Subject(s) - mitochondrial myopathy , kearns–sayre syndrome , mitochondrial dna , lactic acidosis , heteroplasmy , melas syndrome , point mutation , myopathy , biology , nonsense mutation , genetics , ophthalmoparesis , mutation , medicine , endocrinology , gene , ataxia , missense mutation , neuroscience
A 35‐year‐old woman with features of Kearns‐Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type I1 (Addison's disease, autoimmune insulin‐dependent diabetes meuitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532‐bp deletion of the type seen in Kearns‐Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA‐Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large‐scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, largescale mtDNA deletions.