A cluster of metabolic defects caused by mutation in a mitochondrial tRNA

作者：Wilson FH; Hariri A; Farhi A; Zhao HY; Petersen KF; Toka HR; Nelson Williams C; Raja KM; Kashgarian CM; Shulman GI; Scheinman SJ; Lifton RP^*

来源：Science, 2004, 306(5699): 1190-1194.

DOI：10.1126/science.1102521

Hypertension and dyslipidemia are risk factors for atherosclerosis and occur together more often than expected by chance. Although this clustering suggests shared causation, unifying factors remain unknown. We describe a large kindred with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia. Each phenotype is transmitted on the maternal lineage with a pattern indicating mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal lineage identified a homoplasmic mutation substituting cytidine for uridine immediately S'; to the mitochondrial transfer RNA(Ite) anticodon. Uridine at this position is nearly invariate among transfer RNAs because of its role in stabilizing the anticodon loop. Given the known loss of mitochondrial function with aging, these findings may have implications for the common clustering of these metabolic disorders.

• 出版日期2004-11-12