Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie α₂ 130 Ala → Pro and Hb Caserta α₂ 26 Ala → Thr) in a single HBA2 gene

Abstract

Summary This study describes a new molecular condition in the α2‐globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G→A (Hb Caserta) and HBA2 130 G→C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an α‐thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with α° delectional thalassemia.

Effect of Mutations on mRNA and Globin Stability: The Cases of Hb Bernalda/Groene Hart and Hb Southern Italy

“…The Hb Southern Italy showed in Campania a frequency of 3.2% increasing to 20.0% when taking into account the point mutants, only; in Sicily the double mutants showed a lower frequency of 0.5% and 1.6%, respectively. The data on the two clusters of families is confirmed by others authors, one describing the Hb Southern Italy, in three families from Campania and three from Sicily, respectively, and the second describing it in a single subject from Sicily [31,32]. Moreover, two of the patients from Sicily were homozygotes for the Hb Sun Prairie, confirming the presence of a cluster of families [31].…”

“…The data on the two clusters of families is confirmed by others authors, one describing the Hb Southern Italy, in three families from Campania and three from Sicily, respectively, and the second describing it in a single subject from Sicily [31,32]. Moreover, two of the patients from Sicily were homozygotes for the Hb Sun Prairie, confirming the presence of a cluster of families [31].…”

α-Thalassemia Mutation Analyses in Mazandaran Province, North Iran

“…The same two mutations in coexistence were (5). Interestingly, Passarello et al (14) recently described the same condition in six unrelated families from Campania and Sicily; they named this double mutant allele Hb Southern Italy (on the a2 gene). We are currently carrying out family studies to ascertain that, in our patients, the two mutations are also coexisting in cis within a single a2 gene.…”

Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie α2 130 Ala > Pro and Hb Caserta α2 26 Ala > Thr) in a single HBA2 gene

“…Passarello et al (2008) have recently reported as a new finding an allele of the HBA2 gene showing the association of the mutation Hb Caserta with the Hb Sun Prairie and with the single nucleotide polymorphism (SNP) G > A in position +861. The carriers had alpha‐thalassaemia phenotype, the homozygotes had a severe phenotype.…”

“…Passarello et al (2008) gave as a reference – instead of our publications – an old article (Ventruto et al , 1964) describing a haemoglobin variant named Hb Caserta and defined as β‐variant by the authors. The fingerprinting of this haemoglobin and the dissociation/reassociation experiments at pH 4·7 had shown that the alpha chains were normal, but studies for the definition of the beta chain alterations were unsuccessful (Ventruto et al , 1965; Quattrin et al , 1970).…”