Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features

We characterized mutations and haplotypes of the δ‐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. Hum Mutat 20:358–367, 2002. © 2002 Wiley‐Liss, Inc.