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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
Author(s) -
MIRAGLIA del GIUDICE Emanuele,
VALLIER AgnÉs,
MAILLET Philippe,
PERROTTA Silverio,
CUTILLO Stefano,
IOLASCON Achille,
TANNER Michael J. A.,
DELAUNAY Jean,
ALLOISIO Nicole
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.8732504.x
Subject(s) - hereditary spherocytosis , compound heterozygosity , band 3 , genetics , allele , biology , locus (genetics) , heterozygote advantage , microbiology and biotechnology , gene , membrane protein , membrane
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.