title: A new mitochondrial DNA deletion associated with diabetic amyotrophy, diabetic myoatrophy and diabetic fatty liver.
abstract: Mitochondrial dysfunctions of the muscle in diabetic amyotrophy and of the liver in diabetic fatty liver have been reported. We investigated mitochondrial gene mutations in three cases: (1) a patient with diabetic amyotrophy in the muscles of the lower extremities, and neuropathy; (2) 5 diabetics with myoatrophy, diabetic nephropathy, and chronic renal failure; and (3) an IDDM patient with a diabetic fatty liver. We identified a 5778-bp deletion (8214-13991) in mitochondrial DNA from the muscle and liver biopsy specimens by the primer shift PCR and PCR-direct sequence methods. It is speculated that 5778-bp deletion is due to homogeneous recombination in the 7-bp repeat sequence of TCCTAGA flanking the region deleted in the mitochondrial DNA. Determination of respiratory chain enzyme activities in fresh muscle mitochondria demonstrated the defect in complex I activity. The deletion covers areas coding ND3, ND4, ND4L, and ND5 in complex I. The 5778-bp deletion might cause a defect in mitochondrial oxidative phosphorylation and contribute to the pathogenesis of diabetic amyotrophy, myoatrophy with diabetic nephropathy, and chronic renal failure, as well as diabetic fatty liver in IDDM.
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hinokio
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Komatu
authors.forename: M
authors.initials: M
authors.lastname: Ohtomo
authors.forename: M
authors.initials: M
authors.lastname: Onoda
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Hirai
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Akai
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000293:Adolescent; D000368:Aged; D001483:Base Sequence; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009468:Neuromuscular Diseases / Q000209:etiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial