The present paper reports the incidence from 1965 to 1979 of acute hemolytic anemia for a total of 948 cases in G-6-PD-deficient subjects due to the ingestion of fresh or dried fava beans or certain drugs and to viral infections. The highest percentage of hemolytic crises was due to fresh fava beans (94.4%). No cases of favism were observed in breast-fed babies whose mothers had eaten fava beans or from pollen inhalation. The male sex proved to be the hardest hit. Hemoglobin values were lower than or equal to 7 g/dl in about 75% of males and 50% of females. Total bilirubin values were lower than 103 μmol/l (6 mg/dl) in about 75% of males and 85% of females. Both the hemoglobin and bilirubin values were statistically significant. Mean transaminase values (SGPT) were significantly higher than those of normal controls. No correlation between favism and blood groups was found.

Summary.We report three novel variants of band 3 associated with hereditary spherocytosis: band 3 Foggia (311delC; ACCCAC → ACCAC), band 3 Napoli I (447insT; TCT → TTCT) and band 3 Napoli II (I783N; ATC → AAC). The first two mutations resulted in premature termination of translation, making one haploid set of band 3 mRNA unavailable. Since it affected a highly conserved position at the terminal end of transmembrane domain 11, the third mutation prevented one haploid set of band 3 from becoming incorporated or stabilized into the membrane. These three mutations resulted in a reduction of the band 3 level in the red cell membrane (by 20-25%) and were dominantly transmitted. The D38A substitution (GAC → GCC) is a low frequency change of band 3. In one compound heterozygote D38A/Napoli II, a markedly aggravated picture required early splenectomy. In contrast, the D38A change was not associated with deterioration in another compound heterozygote, carrying in trans, the previously recorded R760W mutation (CGG → TGG). In the aggravated case, SSCP analysis did not exhibit any additional change in the two EPB3 alleles. Nor did it show any alteration in the exons of the two ANK1 alleles, and the aggravating factor remained elusive. The D38A alteration should be regarded as an innocuous polymorphism.Keywords: hereditary spherocytosis, band 3, EPB3 gene, mutations, polymorphism.Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia characterized by spheroidal, osmotically fragile, erythrocytes (for review, see Lux & Palek, 1995). The primary molecular defect can reside in several red cell membrane structural proteins: spectrin, ankyrin, band 3 and protein 4.2. Band 3, or the anion exchanger 1 (AE1), is the most abundant protein of the red cell membrane (1 : 2 × 10 6 monomers per cell) and consists of two domains with distinct functions (for review, see Tanner, 1993). The cytoplasmic domain (residues 1-403) binds a number of proteins including ankyrin and protein 4.2. The membrane domain (residues 404-883) harbours 14 membrane-spanning segments (TM) and mediates chloride-bicarbonate passive antiport. Band 3 cDNA has been entirely sequenced (Tanner et al, 1988;Lux et al, 1989;Schofield et al, 1994), and the structure of the band 3 gene (EPB3) has been determined (Schofield et al, 1994;Sahr et al, 1994). Approximately 20% of HS cases are associated with a substantial reduction of the band 3 amount in the red cell membrane (20-40%). Basically, their inheritance pattern is autosomal dominant and their clinical phenotype is mild to moderate in the heterozygous state. Band 3 deficiency is accompanied by a roughly proportional reduction in protein 4.2. Several mutations leading to band 3 reduction and HS have been recently identified. They include (i) mutations producing premature termination of translation (at any position along the whole coding sequence) and (ii) substitutions of highly conserved amino acids within the membrane domain, especially in the last membrane spanning segments (TM9-TM14) or at their bounda...

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This report represents an attempt to define the rate of beta-spectrin de novo mutations affecting mRNA accumulation in patients with hereditary spherocytosis (HS). 19 HS children with haematologically normal parents and varying degrees of spectrin deficiency were studied. 13 of the 19 cases who were heterozygous at the genomic level for polymorphisms in the beta-spectrin coding region were further studied. However, in an analysis of reverse-transcripted amplified cDNA from the regions of the polymorphisms, seven patients appeared to be homozygous, suggesting the occurrence of de novo mutational events affecting expression of one beta-spectrin allele. We conclude that in HS patients with isolated spectrin reduction and normal parents the apparently recessive pattern of inheritance may frequently be associated with de novo monoallelic expression of beta-spectrin.

We describe three Italian subjects from two unrelated families affected with isolated hereditary spherocytosis (HS) without other clinical abnormalities, associated with partial spectrin and ankyrin deficiency. In both families the propositus has normal biological parents, and thus appears to be the result of a new mutation; in one of them the disease is further transmitted in an autosomal dominant fashion. Cytogenetic analysis of the latter family excluded abnormalities of the short arm of chromosome 8. We speculate that in both kindreds ankyrin deficiency is the primary defect related to ankyrin gene mutation. Several pieces of evidence suggest that ankyrin deficiency is probably the most common molecular defect in HS. It is inherited in a, dominant manner and its clinical and biochemical expression is heterogenous.