Molecular screening and fetal diagnosis of ?-thalassemia in the Italian population

Abstract

This paper reports our experience of molecular screening and fetal diagnosis of beta-thalassemia in 457 at risk couples of Italian descent. Molecular screening was carried out by dot blot analysis on amplified DNA with oligonucleotide probes complementary to the eight most common mutations in Italians [beta zero 39 (C----T); beta zero 6 (-A); beta+ -87 (C----G); beta+ IVSI nt 110 (G----A); beta zero IVSI nt 1 (G----A); beta+ IVSI nt 6 (T----C); beta zero IVSII nt 1 (G----A); beta+ IVSII nt 745 (C----G)]. By using this approach, we have been able to define the mutation in 92.8% of cases. The rest (all but four) were defined by direct sequencing and this led to the detection of nine rare mutations [beta zero 76 (-C); beta+ IVSI nt 5 (G----A); beta+ IVSI nt 5 (G----C); beta+ IVSI -1 (cod 30) (G----C); beta+ -87 (C----T), beta zero -290 bp del.; beta+ -101 (C----T)], and to the characterization of a novel mutation consisting of the deletion of the G at the invariant AG of the IVSII splice acceptor site of the beta-globin gene (beta IVSII nt 850 -1 bp). In the remaining four cases, the beta-globin gene showed entirely normal sequences and the beta-globin gene cluster was intact, as indicated by Southern blot analysis. Fetal diagnosis was carried out by dot blot analysis with the oligonucleotide probes defined in the parents. The procedure is simple and reliable, and the results can be obtained within 1 week of sampling. No misdiagnosis has so far occurred. The results indicate that fetal diagnosis of beta-thalassemia by DNA analysis may be obtained in practically all cases (even in a population showing marked heterogeneity of beta-thalassemia) by the combination of dot blot analysis for detecting common mutations, and direct sequencing for defining those that are uncommon.

Molecular Characterization and Phenotypical Study ofβ-Thalassemia in Tucumán, Argentina

“…IVS-I-110 was most prevalent in countries on the eastern shore of the Mediterranean, where Turkey (35.3%) (31), Lebanon (34.2%) (32) and Cyprus (74.0-80.0%) (33) displayed the highest frequencies. Codon 39 occurred in 40.0% of b-thal from the western part of the Mediterranean Basin (34). In the middle of the Mediterranean area, both mutations showed similar frequencies (35).…”

Pregnancy in women with thalassemia: challenges and solutions

“…The risk of miscarriage does not differ between these invasive procedures, and is estimated to be less than 1%. 54 – 59 …”

The Molecular Basis of α Thalassemia

“…In all these cases mutations are of  0 -type and result in severe thalassemia;  protein instability, if they give rise to truncated or elongated globin chains which tend to form insoluble tetrameters. (Rosatelli et al, 1992).…”

“…On the other hand, as the result of mass migration of populations from areas at high risk, hemoglobinopathies are being seen with increasing frequency even in regions where they were rather uncommon. In Italy eight point mutations represent about 90% of -thalassemia defects (Rosatelli et al, 1992) with the remaining 10% being represented by a wide array of molecular defects, some of which very rare. Furthermore, recent intensive immigration flows moving from countries with high incidence of hemoglobinopathies (Middle East, Southeast Asia and Northern Africa) with their own specific pattern of mutations as well, has rapidly increased the molecular heterogeneity of hemoglobinopathies in our region.…”