Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness

JMW Van den Ouweland, H Lemkes, W Ruitenbeek… - Nature …, 1992 - nature.com
JMW Van den Ouweland, H Lemkes, W Ruitenbeek, LA Sandkuijl, MF De Vijlder…
Nature genetics, 1992nature.com
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 …
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 tRNALeu(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.
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