PubMed:9463309 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/9463309","sourcedb":"PubMed","sourceid":"9463309","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9463309","text":"The haptoglobin-gene deletion responsible for anhaptoglobinemia.\nWe have found an allelic deletion of the haptoglobin (Hp) gene from an individual with anhaptoglobinemia. The Hp gene cluster consists of coding regions of the alpha chain and beta chain of the haptoglobin gene (Hp) and of the alpha chain and beta chain of the haptoglobin-related gene (Hpr), in tandem from the 5' side. Southern blot and PCR analyses have indicated that the individual with anhaptoglobinemia was homozygous for the gene deletion and that the gene deletion was included at least from the promoter region of Hp to Hpr alpha but not to Hpr beta (Hpdel). In addition, we found seven individuals with hypohaptoglobinemia in three families, and the genotypes of six of the seven individuals were found to be Hp2/Hpdel. The phenotypes and genotypes in one of these three families showed the father to be hypohaptoglobinemic (Hp2) and Hp2/Hpdel, the mother to be Hp2-1 and Hp1/Hp2, one of the two children to be hypohaptoglobinemic (Hp2) and Hp2/Hpdel, and the other child to be Hp1 and Hp1/Hpdel, showing an anomalous inheritance of Hp phenotypes in the child with Hp1. The Hp2/Hpdel individuals had an extremely low level of Hp (mean+/-SD = 0.049+/-0. 043 mg/ml; n=6), compared with the level (1.64+/-1.07 mg/ml) obtained from 52 healthy volunteers having phenotype Hp2, whereas the serum Hp level of an individual with Hp1/Hpdel was 0.50 mg/ml, which was approximately half the level of Hp in control sera from the Hp1 phenotype (1.26+/-0.33 mg/ml; n=9), showing a gene-dosage effect. The other allele (Hp2) of individuals with Hp2/Hpdel was found to have, in all exons, no mutation, by DNA sequencing. On the basis of the present study, the mechanism of anhaptoglobinemia and the mechanism of anomalous inheritance of Hp phenotypes were well explained. However, the mechanism of hypohaptoglobinemia remains 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