title: HbA2-Partinico or delta(A2)Pro-->Thr, a new genetic variation in the delta-globin gene in cis to the beta(+) thal IVS-I-110 G>A, and the heterogeneity of delta-globin alleles in double heterozygotes for beta- and delta-globin gene defects.
abstract: The study of the alleles of the delta-globin gene is relevant to the prevention of beta-thalassemia homozygosis; in fact, the increase of the HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and the double heterozygosis for alleles of delta- and beta-globin genes can cause the decrease of the HbA2 up to normal or borderline values. We carried out the characterization of alleles of the delta- and beta-globin genes, restriction fragment length polymorphism (RFLP) haplotype background, and hematologic phenotype in 23 double heterozygotes belonging to 18 unrelated families. A wide heterogeneity of the delta-globin alleles was detected; seven known alleles in trans to the beta-globin gene defects were revealed in 17 out of 18 families, while a new allele in cis to a beta-thalassemia allele was detected in one family. Moreover, the relative frequency of the delta-mutants was quite different from that found among heterozygotes. The new allele delta-cod 5 CCT>ACT, in cis to the allele beta(+) thal IVS-I-110 G>A, was found in five carriers of a Sicilian family. The new variant delta5(A2)Pro-->Thr, named HbA2-Partinico upon the origin of the family, was detected with high-performance liquid chromatography; it overlapped the HbA2 peak which was partially split. The double in cis heterozygotes had increased percentage of normal and variant HbA2 of comparable size. The variant originated most likely from a new mutational event because it was associated with RFLP haplotype I, commonly found with the beta(+) thal IVS-I-110 G>A, even if crossing over or gene conversion cannot be excluded.
authors.affiliation: Istituto di Genetica e Biofisica "Adriano Buzzati Traverso", CNR, Via Pietro Castellino 111, 80131, Naples, Italy. lacerra@igb.cnr.it
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lacerra
authors.forename: Clelia
authors.initials: C
authors.lastname: Scarano
authors.forename: Gennaro
authors.initials: G
authors.lastname: Musollino
authors.forename: Rosario
authors.initials: R
authors.lastname: Testa
authors.forename: Romeo
authors.initials: R
authors.lastname: Prezioso
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Caruso
authors.forename: Laura F
authors.initials: LF
authors.lastname: Lagona
authors.forename: Emilia
authors.initials: E
authors.lastname: Medulla
authors.forename: Maria G
authors.initials: MG
authors.lastname: Friscia
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudiano
authors.forename: Clementina
authors.initials: C
authors.lastname: Carestia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*; D055546:delta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins; D055546:delta-Globins