title: Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features.
abstract: We characterized mutations and haplotypes of the delta-globin gene (HBD, MIM# 142000) in two regions of southern Italy. Mutations were discovered by screening for individuals with Hb A2<2%. In Basilicata, about 10,000 students were screened and 53 carriers in 43 unrelated families were diagnosed; in Campania, cases were referred through a routine thalassemia counseling service. Twelve alleles were detected. Four were novel variants [Hb A2-Metaponto (g.238C>A), Hb A2-Campania (g.302C>A), Hb A2-Lucania (g.393C>G), and Hb A2-Capri (g.443G>T)]. Hb A2-Lucania was not inherited but had arisen in the propositus. Two were novel mutations in the noncoding regions: the substitutions IVS2+6T>A, presumably affecting the splicing, and g.-126A>T in the GATA motif presumably affecting transcription. All novel alleles were found associated with haplotypes common in the Mediterranean area. The remaining six were alleles already described. The Hb A2-Yialousa (g.82G>T) was the most prevalent (42/63 families). Recurrent homologous crossing-over events have, most likely, linked this allele to Haplotypes IX (24 families), IV (10 families), or III (seven families). The ratio of Haplotypes IX:IV:III was about the same in the two regions. The rare allele Hb A2-NYU (g.39T>A) was found in 11 families from Basilicata associated with Haplotype I. All the 11 families lived in a restricted area extending from the Ionian Coast for 15 km along the Angri and Sinni Rivers. A founder effect most probably gave origin to this isolated group. The remaining four alleles were rare: the 7.2-kb deletion Corfù type (HBD g.-5946_1262del), Hb A2-Mitsero (g.14C>T), Hb A2-Etolia (g.385T>C), Hb A2-Coburg (g.1376G>A). Correlation between genotype and phenotype was established in 103 carriers.
authors.affiliation: Istituto di Genetica e Biofisica Adriano Buzzati Traverso, Napoli, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Angioletti
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lacerra
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaudiano
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mastrolonardo
authors.forename: Leonilde
authors.initials: L
authors.lastname: Pagano
authors.forename: Lucia
authors.initials: L
authors.lastname: Mastrullo
authors.forename: Santa
authors.initials: S
authors.lastname: Masciandaro
authors.forename: Clementina
authors.initials: C
authors.lastname: Carestia
mesh_terms: D000483:Alleles; D001483:Base Sequence; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006454:Hemoglobins / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D013789:Thalassemia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D005914:Globins