The mitochondrial DNA A8344G mutation in Leigh syndrome revealed by analysis in paraffin-embedded sections: revisiting the past.
In 1975, we presented the results of a study on a family with a constellation of features that included a chronic spinocerebellar syndrome, neuropathologically proven Leigh syndrome, and sudden death in infancy or childhood affecting several members over three generations. Inheritance was thought to be autosomal dominant. Twenty years later, we reinterpreted the inheritance pattern as maternal. Mitochondrial DNA (mtDNA) extracted from paraffin-embedded brain samples from the proband revealed the A8344G myoclonic epilepsy and ragged-red fiber (MERRF) mutation as the molecular basis for this multifaceted neurological syndrome. This re-evaluation of archival material is an instructive example of "medical archeopathology."
Santorelli
F M
FM
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia University, New York, NY, USA.
Tanji
K
K
Shanske
S
S
Krishna
S
S
Schmidt
R E
RE
Greenwood
R S
RS
DiMauro
S
S
De Vivo
D C
DC
D000293:Adolescent; D000328:Adult; D001109:Archives; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007888:Leigh Disease / Q000235:genetics*; D017243:MERRF Syndrome / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D016612:Paraffin Embedding; D010375:Pedigree
D004272:DNA, Mitochondrial