Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus

• Published in: British journal of haematology Vol. 96; no. 1; pp. 70 - 76
• Main Authors: MIRAGLIA del GIUDICE, Emanuele, VALLIER, AgnÉs, MAILLET, Philippe, PERROTTA, Silverio, CUTILLO, Stefano, IOLASCON, Achille, TANNER, Michael J. A., DELAUNAY, Jean, ALLOISIO, Nicole
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.1997; Blackwell
• Subjects: Anemias. Hemoglobinopathies; Anion Exchange Protein 1, Erythrocyte - genetics; band 3; Biological and medical sciences; Diseases of red blood cells; DNA Mutational Analysis; EPB3 gene; Erythrocyte Membrane - chemistry; Female; Gene Deletion; Genes, Dominant; Hematologic and hematopoietic diseases; hereditary spherocytosis; Humans; Male; Medical sciences; Membrane Proteins - analysis; Mutation; mutations; Nucleic Acids - analysis; Pedigree; polymorphism; Polymorphism, Genetic; Spherocytosis, Hereditary - genetics; Human; Erythrocytic membrane disease; Band 3 protein; Hemolytic anemia; Gene; Pathogenesis; Deficiency; Genetic variant; Hemopathy; Spherocytic anemia; Mutation; Genetic disease
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.1997.8732504.x

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.