BAND-4.2-SHIGA - 317-CGC-]TGC IN COMPOUND HETEROZYGOTES WITH 142-GCT-]ACT RESULTS IN BAND-4.2 DEFICIENCY AND MICROSPHEROCYTOSIS

A novel compound heterozygous mutations of 317 CGC --> TGC with 142 GC T --> ACT in human red cell band 4.2 deficiency is described. A proban d and his son suffered from compensated haemolysis with nearly complet e deficiency of red cell band 4.2. Their red cell morphology exhibited microspherocytosis resembling classic hereditary spherocytosis (HS). Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) s howed ban 4.2 to be nearly missing (<1% of normal controls) with th pr esence of 74 kD and 72 kD isoforms in trace amounts. Other family memb ers (daughters older and younger than the son) exhibited nearly normal amounts of 72kD as a wild form of band 4.2 on SDS-PAGE with the prese nce of the 74 kD isoform in an trace compound heterozygous mutations i n trans: i.e. nucleotide (nt) 949 CGC --> TGC (codon 317 AR --> Cys) i n exon 7 and nt 424 GCT --> ACT ( codon 142 Ala --> Thr) in exon 3 of the band 4.2 gene. The two daughters demonstrated only the mutation of nt 949 CGC --> TGC in exon 7 in heterozygous states, but no 142 mutat ion. Therefore the proband and his son were compound heterozygotes of these two mutations in trans. It is interesting to not that the 74 kD isoform of band 4.2 protein existed in a trace amount in the two daugh ters in spite of the absence of the 142 Ala --> Thr mutation. In addit ions, even in the presence of the 142 mutation in one allele in the pr oband and his son, their red cell morphology demonstrated classic HS w ith microspherocytosis, although a homozygous state of the 142 mutatio n known as the Nippon type of band 4.2 deficiency exhibits ovalostomat ocytosis.