title: Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.
abstract: Non-insulin-dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNA(Leu)(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM.
authors.affiliation: Department of Medical Biochemistry, Sylvius Laboratories, Leiden, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van den Ouweland
authors.forename: H H
authors.initials: HH
authors.lastname: Lemkes
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: L A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: M F
authors.initials: MF
authors.lastname: de Vijlder
authors.forename: P A
authors.initials: PA
authors.lastname: Struyvenberg
authors.forename: J J
authors.initials: JJ
authors.lastname: van de Kamp
authors.forename: J A
authors.initials: JA
authors.lastname: Maassen
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification; D003638:Deafness / Q000150:complications / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D004272:DNA, Mitochondrial; D009838:Oligodeoxyribonucleotides; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D012313:RNA