PRENATAL DIAGNOSIS OF β-THALASSEMIA IN EGYPT: Implementing Accurate High-Tech Methods Did not Reflect Much on the Outcome

Abstract

The clinical severity of thalassemia major makes it a priority genetic disease for prevention programs through prenatal diagnosis for carrier couples. Incorporation of automated DNA sequencing that enables the characterization of mutations not detected by other mutation specific detection procedures was a prime goal of this work. Automated DNA sequencing was offered on fetal tissues in 30 pregnancies during the year 2005. The pregnancies were at high risk for homozygosity or compound heterozygosity for beta-thalassemia based on mutation analysis of both parents before prenatal diagnosis. Both parents have beta-thalassemia trait. Fetal samples were collected by chorionic villus sampling (CVS) in the first trimester and by amniocentesis in the second trimester. The point mutations were characterized by PCR (ARMS). The absence of the expected fragment with all the mutant ARMS primers insinuated an uncharacterized DNA segment that was further subjected to direct automated fluorescent DNA sequencing in an attempt to know if the fetus was affected by parents' mutations. If no mutation was detected using the PCR ARMS, the sample was further analyzed using direct automated fluorescent DNA sequencing. The mean gestation when carrying out the invasive procedure was 14 (10 -18) weeks. All mothers had a previous affected pregnancy, and 13 had two or more previous affected pregnancies. Pregnancies were: 8 carrier fetuses (trait) and 22 affected fetuses in which 2 were homozygous and 20 double heterozygous. Fourteen parents of affected fetuses preferred to continue pregnancy and the babies were born as diagnosed. The other 8 parents decided on termination and DNA of the abortuses proved to be as previously diagnosed by DNA sequencing. The use of PCR amplification and direct sequencing have permitted the accurate characterization of unidentified alleles and successfully solved 100% of the examined samples. However, it has resulted in minor changes of the outcome as the majority of couples preferred continuation of pregnancy.

Prenatal diagnosis for thalassaemia in Egypt: what changed parents' attitude?

“…In a previous report from Egypt, only 36% of pregnant mothers with affected fetuses elected to terminate their pregnancy despite being counseled about the hazards of having an affected child and the often poor prognosis in Egypt. These couples were well aware of the complications of thalassaemia major as they already had at least one affected live child …”

“…Educational programs for the patients and their parents have been conducted on a limited scale . Although prenatal diagnosis of β‐thalassaemia has been previously conducted in Egypt in at‐risk pregnancies, the majority of the couples continued the affected pregnancy despite knowledge of the hazards of an affected child in Egypt …”

Epidemiological profile of common haemoglobinopathies in Arab countries

“…The mean gestation period at the time of PND was 14 (10-18) weeks. All mothers had a previous affected pregnancy, and 13 had two or more previous affected pregnancies (Elgawhary et al 2008). On the other hand, a more recent study presenting the current status of the PND services and results from the largest thalassaemia centre in Egypt treating 3,000 patients showed that all 24 women who underwent prenatal testing and received a diagnosis that the foetus is affected by β-thalassemia major opted for pregnancy termination.…”

The first five years of a preventive programme for haemoglobinopathies in Northeastern Iraq

“…The almost universal choice to terminate by the couples with affected fetuses is consistent with that reported from many countries, 26,30,[32][33][34] with rare exceptions. 35 Improvements to our programme are still needed, including establishing better contact with the couples at risk (with periodic follow up), improving the genetic counselling to ensure a higher uptake of PND, upgrading and intensifying the population education programmes, offering voluntary haemoglobinopathy screening to couples married prior to 2008, and establishing better awareness among the thalassaemic families of the value of PND to prevent the birth of further affected children.…”