Biochemical studies on red blood cells from a patient with the Inab phenotype (decay-accelerating factor deficiency)

Abstract

A 38-year-old Russian woman (KZ) has been identified as the fourth proposita with the Inab blood group phenotype. Like the first two propositi, she has a chronic intestinal disorder and, as shown for the third proposita, her Inab phenotype is demonstrably inherited. KZ's serum contained anti-IFC, which reacted with a red blood cell (RBC) membrane component with an Mr of 70,000, which is decay accelerating factor (DAF). Her RBCs lacked all Cromer-related blood group antigens and DAF. Her RBCs were no more susceptible than normal control RBCs to lysis in acid lysis or in rabbit or human antibody-initiated complement lysis tests. Northern blots of total RNA isolated from KZ's Epstein- Barr virus-transformed lymphoblasts showed a marked reduction of DAF mRNA when compared with normal. Polymerase chain reaction (PCR) amplification of cDNA confirmed this reduced level of DAF mRNA. Sequencing of the PCR product showed a 44-nucleotide deletion in the mRNA close to the short consensus repeats IIIa/IIIb intron/exon boundary. This deletion results in a change in the reading frame that places a termination codon six amino acids after the deletion. The putative translation product would lack a glycosyl phosphatidyl- inositol linkage site and, therefore, would not be membrane-bound in the RBC.

Application of flow cytometry to the diagnosis of paroxysmal nocturnal hemoglobinuria

“…This is because rare hereditary deficiencies of the individual complement regulatory molecules CD55 and CD59 can occur. In contrast to the majority of PNH cases, all cells in these patients are either CD55 or CD59 deficient (42, 43).…”

“…Deficiency of at least two GPI‐linked antigens (CD55 and CD59) should be demonstrated from red cells as single‐antigen deficiencies have been reported as rare inherited conditions (42, 43). Red cell analysis provides the clearest discrimination between types I, II, and III cells and may predict clinical phenotype (70).…”

Case report and literature review: transient Inab phenotype and an agglutinating anti‐IFC in a patient with a gastrointestinal problem

“…Second, reduced Cromer system antigen expression occurs in the case of the rare Dr(a–) RBCs 10 . The molecular basis for this phenotype is a single‐nucleotide polymorphism (SNP) in exon 5 of DAF , 596C>T, which results in alternative splicing of the DAF mRNA such that the resulting major transcript lacks 44 nucleotides 10‐12 . In addition, this alternative splicing shifts the reading frame and introduces a premature stop codon; the translated protein cannot attach to the membrane and is not present on the membrane of the RBCs 12 .…”

“…The molecular basis for this phenotype is a single‐nucleotide polymorphism (SNP) in exon 5 of DAF , 596C>T, which results in alternative splicing of the DAF mRNA such that the resulting major transcript lacks 44 nucleotides 10‐12 . In addition, this alternative splicing shifts the reading frame and introduces a premature stop codon; the translated protein cannot attach to the membrane and is not present on the membrane of the RBCs 12 . A small minority of the DAF mRNA transcripts, however, contain this SNP but do not utilize the cryptic splice acceptor site 13 .…”

A Minimally Invasive Blood‐Extraction System: Elastic Self‐Recovery Actuator Integrated with an Ultrahigh‐ Aspect‐Ratio Microneedle

“…Blood is a rich source of biological information, and blood analysis is critical to the diagnosis of many human diseases 1. Blood is generally obtained from arm veins by a hypodermic needle or a finger‐prick 2.…”