Antenatal Diagnosis of β‐Thalassemia in Sardinia^a

Abstract

This paper reviews the characteristics and the results of 15 years of experience with a preventive program, based on carrier screening and prenatal diagnosis, designed to control thalassemia major in the Sardinian population. The education of the population about thalassemia and the modalities for its prevention was accomplished via the mass media. Carrier screening was carried out voluntarily on couples of child-bearing age. Prenatal diagnosis was initially carried out by fetal blood analysis; since 1983, it has been done by DNA analysis on non-amplified or amplified DNA. Different chorionic villous sampling procedures have been used. Nowadays, we have adopted the transabdominal approach because, in our experience, it seems to be associated with a low risk (2%) of fetal mortality. At the present time, the beta-thalassemia mutations are detected directly by dot-blot analysis of amplified DNA with 32P- or horseradish peroxidase-labeled allele-specific oligonucleotide probes. Two oligonucleotide probes, one complementary to the codon-39 nonsense mutation, which accounts for 95.7% of the beta-thalassemia chromosomes in the Sardinian population, and the other complementary to the frameshift at codon 6, which is the second most common mutation in our population (2.1%), allow us to make prenatal diagnosis in the large majority of cases. Notwithstanding a careful dissection of maternal decidua from chorionic villi, co-amplification of maternal sequence was detected in 4 out of 425 cases tested by this procedure. In order to avoid this pitfall, the simultaneous amplification of highly polymorphic VNTR (variable number of tandem repeats) segments could be used. On the whole we have so far carried out 2711 prenatal tests: 1130 by fetal blood analysis, 1156 by oligonucleotide hybridization on electrophoretically separated DNA fragments, and 425 by dot-blot analysis on amplified DNA with allele-specific oligonucleotide probes. Two errors occurred by fetal blood analysis and none by DNA analysis. The incidence of thalassemia major declined from 1:250 live births in the absence of prevention to 1:1000 after the establishment of this program, indicating that carrier screening and prenatal diagnosis are effective means for preventing thalassemia major at the population level.

After the Introduction into the National Newborn Screening Program: Who Is Receiving Genetic Counseling for Hemoglobinopathies in The Netherlands?

“…All these possible misunderstandings are in contrast with data from this study and enquiries made among populations at risk showing that at least 80% of the well-informed multi-ethnic people in The Netherlands would choose for counseling and prevention in case of increased risk [18]. Additionally, many studies in other European, (North- and South) American and Islamic countries have shown a decrease in the number of affected children after proper information and counseling [19,20,21,22,23,24,25,26]. …”

?-globin gene cluster haplotypes associated with ?-thalassemia on Corsica island

“…The b + IVS-1 nucleotide 110 seems to be prevalent in the eastern part of the Mediterranean area, including Turkey [10], Lebanon [11], and Egypt [12]. On the other hand, the b 0 -39 mutation is almost exclusive to Sardinia [13]. It is also highly prevalent in Italy [14] and Spain [15] and is frequently encountered in Portugal [16,17] and Tunisia [18].…”

Molecular Defects in Beta-Thalassaemia in the Population of Saudi Arabia

“…This aspect is of particular im portance for carrier detection, genetic coun selling and prenatal diagnosis. Prevention of the disease can be achieved sucessfully by genetic counselling and prenatal diagnosis, as was shown to be the case in Sardinia, Cyprus and Greece [8][9][10], In Saudi Arabia, the P-thalassaemias, first reported in 1976, exhibit a high, but variable, prevalence in different parts of the country [11][12][13], The clinical presentation seems to resemble that reported in other populations, but the molecular defects have not yet been elucidated. In this study, we investigated twenty mutations commonly reported in the Asian, Mediterranean and Chinese popula tions, to determine the frequency of each in an attempt to identify the ethnic-group-specific alleles in the Saudi population.…”