A cluster of metabolic defects caused by mutation in a mitochondrial tRNA.
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 5' to the mitochondrial transfer RNA(Ile) 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.
Wilson
Frederick H
FH
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Hariri
Ali
A
Farhi
Anita
A
Zhao
Hongyu
H
Petersen
Kitt Falk
KF
Toka
Hakan R
HR
Nelson-Williams
Carol
C
Raja
Khalid M
KM
Kashgarian
Michael
M
Shulman
Gerald I
GI
Scheinman
Steven J
SJ
Lifton
Richard P
RP
D000328:Adult; D000375:Aging; D000926:Anticodon; D015992:Body Mass Index; D016000:Cluster Analysis; D003562:Cytidine; D005111:Extrachromosomal Inheritance; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics* / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008274:Magnesium / Q000097:blood* / Q000652:urine; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012313:RNA / Q000235:genetics; D000077278:RNA, Mitochondrial; D012355:RNA, Transfer, Ile / Q000235:genetics*; D013577:Syndrome; D013936:Thymidine; D014529:Uridine
D000926:Anticodon; D000077278:RNA, Mitochondrial; D012355:RNA, Transfer, Ile; D003562:Cytidine; D012313:RNA; D008274:Magnesium; D013936:Thymidine; D014529:Uridine