title: Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions.
abstract: Two anhaptoglobinemic patients showing anaphylactic transfusion reactions by antihaptoglobin antibody were found. Southern blot analysis indicated that 2 patients were homozygous for the deleted allele of the haptoglobin gene (Hp(del)) as reported previously. We have identified the junction region of the deletion from genomic DNA of 1 patient using cassette-mediated polymerase chain reaction (PCR). Then, the deleted region from the 5' breakpoint to the promoter region of the Hp was amplified from genomic DNA of a control individual using PCR. DNA sequence analysis of these regions indicated that the 5' breakpoint of the Hp(del) allele was located 5. 2 kilobase (kb) upstream of exon 1 of the Hp and the 3' breakpoint was positioned between 52 and 53 base pair (bp) upstream of exon 5 of the haptoglobin-related gene. There was no significant homology between the DNA sequences flanking the 5' and 3' breakpoints, except for a 2-bp (TG) identity. To examine the gene frequency, we have developed a simple PCR method to detect the gene deletion. We found 8, 16, and 17 Hp(del) alleles in 157 Koreans, 523 Japanese, and in 284 Chinese, respectively, but did not find the Hp(del) in 101 Africans or in 100 European-Africans. The incidence of individuals homozygous for the Hp(del) allele was therefore expected to be 1/4000 in Japanese, 1/1500 in Koreans, and 1/1000 in Chinese. This incidence is higher than that of IgA deficiency in Japanese. More attention should be paid on haptoglobin deficiency and antihaptoglobin antibody as the cause of transfusion-related anaphylactic reactions in Asian populations. (Blood. 2000;95:1138-1143)
authors.affiliation: Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koda
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Soejima
authors.forename: E
authors.initials: E
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Morishita
authors.forename: S
authors.initials: S
authors.lastname: Moriya
authors.forename: S
authors.initials: S
authors.lastname: Mitsunaga
authors.forename: K
authors.initials: K
authors.lastname: Tadokoro
authors.forename: H
authors.initials: H
authors.lastname: Kimura
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D000707:Anaphylaxis / Q000235:genetics* / Q000276:immunology; D044466:Asian People; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes; D001483:Base Sequence; D002681:China / Q000208:ethnology; D004247:DNA / Q000097:blood; D005091:Exons; D017353:Gene Deletion; D006242:Haptoglobins / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan; D007723:Korea / Q000208:ethnology; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D065227:Transfusion Reaction
chemical_list: D020121:5' Untranslated Regions; D001323:Autoantibodies; D006242:Haptoglobins; D004247:DNA