Clinical and molecular studies in three Portuguese mtDNA T8993G families

The T8993G mutation in the mitochondrial DNA adenosine triphosphatase 6 gen e represents an important cause of maternally inherited Leigh's syndrome. R eported are the clinical findings and mutational loads in three Portuguese T8993G pedigrees, Polymerase chain reaction-restriction fragment length pol ymorphism analyses demonstrated the T8993G mutation in a high percentage of tissues from all patients (97% +/- 2.3%), but it was less abundant in the blood from 14 maternal relatives, The disease progressed severely in the pr obands but did not have the fatal course reported by others. To test whethe r this prolonged course was related to the presence of a specific, disease- associated haplogroup the origin of the mutational event in Portugal was tr aced. Haplotype investigation revealed an independent occurrence of the mut ation in the three probands, These analyses represent the first molecular c haracterization of Portuguese patients with Leigh's syndrome. (C) 2000 by E lsevier Science Inc. All rights reserved.