MOLECULAR AND GENETIC ANALYSES OF 2 PATIENTS WITH PEARSON MARROW-PANCREAS SYNDROME

Pearson's syndrome, a rare and fatal disorder characterized by refract ory sideroblastic anemia and pancreatic insufficiency in infancy, is c lassified into mitochondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochond rial respiratory chain enzymes and the mitochondrial DNA (mtDNA) in tw o Japanese patients with Pearson's syndrome. Immunoblot analysis from various tissues showed the different grades of defects in the subunits of respiratory enzyme complexes. The analyses of mtDNA showed that th e deletion in patient 1 spanned 4977 bp from the ATPase 8 gene to the NADH dehydrogenase 5 gene between 13-bp direct repeats, whereas the de letion in patient 2 spanned 3151 bp from the transfer RNA(His) gene to the cytochrome b gene unrelated to any repeated sequences. The delete d mtDNA was heteroplasmic in all the analyzed tissues, but the proport ions of deleted mtDNA were quite different. We observed a tendency for the tissue with low percentages of normal-sized mtDNA to show low con tents of complex I subunits. Analysis of the entire sequence of both p atient's mtDNA showed several nucleotide substitutions including alter ation of the initiation codon of the NADH dehydrogenase 5 gene. Some o f these nucleotide substitutions might contribute to the phenotypic ex pression of Pearson's syndrome synergistically with the deletion.