Molecular and Genetic Analyses of Two Patients with Pearson's Marrow-Pancreas Syndrome

Pearson's syndrome, a rare and fatal disor- der characterized by refractory sideroblastic anemia and pancreatic insufficiency in infancy, is classified into mito- chondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochondrial respiratory chain enzymes and the mito- chondrial DNA (mtDNA) in two Japanese patients with Pearson's syndrome. Immunoblot analysis from various tissues showed the different grades of defects in the sub- units of respiratory enzyme complexes. The analyses of mtDNA showed that the 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 deletion in patient 2 spanned 3151 bp from the transfer RNA"" gene to the cytochrome b gene unrelated to any repeated sequences. The deleted mtDNA was heteroplasmic in all the analyzed tissues, but the proportions of deleted mtDNA were quite different. We observed a tendency for the tissue with low percentages of normal-sized mtDNA to show low contents of complex I subunits. Analysis of the entire sequence of both patient's mtDNA showed several nucleo- tide substitutions including alteration of the initiation codon of the NADH dehydrogenase 5 gene. Some of these nu- cleotide substitutions might contribute to the phenotypic expression of Pearson's syndrome synergistically with the deletion. (Pediatr Res 34: 105-1 10, 1993) Abbreviations