SPECTRUM OF MITOCHONDRIAL-DNA REARRANGEMENTS IN THE PEARSON MARROW-PANCREAS SYNDROME

The Pearson marrow-pancreas syndrome (MIM 557000) is a disorder involv ing the hematopoietic system and the exocrine pancreas in early infanc y. We have previously shown that this disease results from a defect of oxidative phosphorylation associated with deletions of the mitochondr ial DNA, We present here a series of 21 cases (including 15 unreported patients) with Pearson syndrome and describe mitochondrial DNA deleti ons as consistent features in this syndrome, Nine patients presented t he same 4.9 kb deletion, while other patients presented different dele tions ranging in size from 9 to 14 kb between tRNA(Cyst) and the D-loo p. Direct repeats (4-13 bp) were consistently present in the wild-type mtDNA at the boundaries of the deletions. Deletion-dimers, deletion-m ultimers or duplications were observed in association with deletions, Duplications were identified both in patients who died of their Pearso n syndrome and in the ones who survived and developed Kearns-Sayre syn drome, suggesting that no correlation could be made between the clinic al severity and the type, size or location of the rearrangements.