Deletions of mitochondrial DNA in Kearns-Sayre syndrome and ocular myopathies: genetic, biochemical and morphological studies.
Genetic, biochemical and morphological investigations were conducted on skeletal muscle mitochondria from 6 cases of ocular myopathy: 4 cases with Kearns-Sayre syndrome (KSS) and 2 with chronic progressive external ophthalmoplegia. All of these 6 cases showed mitochondrial DNA (mtDNA) deletions in addition to normal sized DNA in the quadriceps muscle. The deletions ranging from 3 to 8 kbp were also mapped between nucleotides 5500 and 16000 by Southern blot. The deleted genes encoded for some subunits of complexes I, IV, V and 5-10 tRNAS. The boundaries of the deletions have been sequenced in three patients. Five patients had mitochondrial respiratory chain deficiency in complex I as shown by the low oxygen consumption in isolated mitochondria using three NAD(+)-linked substrates. Mitochondria with an abnormal ultrastructure were also observed in 2 cases. A good relationship between the cytochrome c oxidase deficiency and the amount of deleted mtDNA was shown in our present investigations.
Degoul
F
F
INSERM U. 75, Paris, France.
Nelson
I
I
Lestienne
P
P
Francois
D
D
Romero
N
N
Duboc
D
D
Eymard
B
B
Fardeau
M
M
Ponsot
G
G
Paturneau-Jouas
M
M
D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D030401:Cytochrome-c Oxidase Deficiency; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000172:deficiency / Q000235:genetics*; D009132:Muscles / Q000473:pathology; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction; D012343:RNA, Transfer / Q000235:genetics
D004272:DNA, Mitochondrial; D009097:Multienzyme Complexes; D012343:RNA, Transfer; D003576:Electron Transport Complex IV