Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome.

Abstract:

:Pearson's syndrome, a rare and fatal disorder characterized by refractory sideroblastic anemia and pancreatic insufficiency in infancy, is classified into mitochondrial cytopathies. To understand the molecular and genetic bases of this disorder, we have investigated the mitochondrial respiratory chain enzymes and the mitochondrial DNA (mtDNA) in two 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 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(His) 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 nucleotide substitutions including alteration of the initiation codon of the NADH dehydrogenase 5 gene. Some of these nucleotide substitutions might contribute to the phenotypic expression of Pearson's syndrome synergistically with the deletion.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Sano T,Ban K,Ichiki T,Kobayashi M,Tanaka M,Ohno K,Ozawa T

doi

10.1203/00006450-199307000-00024

subject

Has Abstract

pub_date

1993-07-01 00:00:00

pages

105-10

issue

1

eissn

0031-3998

issn

1530-0447

journal_volume

34

pub_type

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