A DELETIONAL FRAMESHIFT MUTATION IN PROTEIN-4.2 GENE (ALLELE-4.2 LISBOA) ASSOCIATED WITH HEREDITARY HEMOLYTIC-ANEMIA

We studied a 26-year-old Portuguese patient with recessively transmitt ed hereditary hemolytic anemia. Protein 4.2 was absent from red cell g hosts by Western blotting. Although the 4.2 mRNA was not detected in N orthern blots, it was shown to be present by a procedure based on nest ed reverse transcription-polymerase chain reaction (RT-PCR). Partial n ucleotide sequencing disclosed a one-nucleotide deletion at nt 264 (or 265): AAG GTG --> AAG TG, in codon 88 (or 89) belonging to exon 2. Th is change, defining allele 4.2 Lisboa, placed in frame the nonsense tr iplet that normally overlaps codons 136 and 137 (GTG ACC). This mutati on, which abolishes an EcoNI sits, was also found in the gene of the p roband (homozygous state), her parents, and her brother (heterozygous state). Apart from anemia, the patient was free of clinical manifestat ions. Platelet membranes were also investigated using Western blots. A ntibodies to red cell protein 4.2 showed a doublet (72 and 70 kD) both in the controls and the patient. This finding raises an interesting q uestion concerning the relationship between this doublet and erythroid protein 4.2. (C) 1995 by The American Society of Hematology.