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We report the spectrum of ββ-thalassemia (ββ-thal) mutations observed in a cohort of at-risk couples, who presented for prenatal diagnosis at the Thalassemia, Hemophilia and Prenatal Diagnosis Genetic Research Center, Shiraz Medical University, Fars, Iran, from March 2001 to April 2002. Using polymerase chain reaction-amplification refractory mutation system (PCR-ARMS), restriction fragment length polymorphism (RFLP) and direct sequencing technologies, in different combinations, we were able to provide preventive medical abortions to 55 couples at-risk of having an affected fetus. Fetal samples of chorionic villus (63.6%%) or amniocentesis (37.6%%) were collected according to the gestational age. The average presentation age was 11.6 ±± 2.6 weeks. The expected prevalent mutations were IVS-II-1 (G>A, 23.6%%) and IVS-I-110 (G>A, 10.0%%) followed by IVS-I-5 (G>C, 6.4%%) and IVS-I, 25 bp deletion (8.2%%). [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the degree of acceptability of prenatal diagnosis and voluntary termination of pregnancy in case of a fetus affected with β-thalassemia major (β-TM) in patients and their parents in Southern Iran. We interviewed 510 parents who had β-TM children and 254 patients. A questionnaire was used to record information regarding sex, age, parents' and patients' knowledge about prenatal diagnosis, and their decision regarding abortion of an affected fetus. Of 764 participants, 565 (73.9%) knew a little about prenatal diagnosis and 198 (25.9%) had no knowledge at all, while 711 (93%) were in favor of prenatal diagnosis and 53 (6.9%) were not. Specifically, 663 subjects (86.7%) were in favor of early termination of pregnancy in case of an affected fetus, while (13.2%) were not. Compliance with prenatal diagnosis was high, and the main reason for declining was its cost. No particular correlations were found between the size of the household, the education or the economic level, and the request for early termination of pregnancy of an affected fetus. The decision not to have a medical abortion correlated with religious beliefs only. [ABSTRACT FROM AUTHOR]

β-Thalassemias are a group of heterogenous recessive disorders common in many parts of the world. Despite the great advances in the treatment of thalassemia, there is so far no cure, but perhaps bone marrow transplantation (BMT) is a possibility. Prevention, using prenatal diagnosis and selective abortion in the cases where the fetus is found to be affected, should be considered as a sensible alternative. During the past 5 years, 112 couples have been referred to our Center for detection of their β-thalassemia (β-thal) carrier status. In this group, common and rare mutations were detected. Of these, 106 couples (94.6%) came for counseling during pregancy and six (5.4%) came before becoming pregnant. Prenatal diagnosis was performed for the 106 couples at risk. Fetal DNA was obtained from both chorionic villus sampling (CVS) (99) and amniotic fluid (7). Using reverse hybridization, 64 (60.4%) were found to be heterozygous for a β-thal mutation and 24 (22.6%) were normal. Eighteen (17.0%) were found to carry an affected fetus and these pregnancies were terminated. [ABSTRACT FROM AUTHOR]

β-Thalassemia (thal) is one of the most common autosomal recessive disorders in Iran. There are more than two million carriers of β-thal and over 15,000 people affected with β-thal major who live in Iran. Prevalent mutations were identified by examining genomic DNAs isolated from 392 blood samples of β-thal carriers from three northern provinces of Iran. Furthermore, 172 pregnant women were analyzed from the 196 couples who requested pregnant diagnosis for β-thal. Allele identification was carried out using routine reverse dot-blot, amplification refractory mutation system (ARMS), and genomic sequencing. The most common mutation, IVS-II-1 (G→A), is followed, in order of frequency, by codon 30 (G→C), frameshift codons (FSC) 8,9 (+G), FSC 22/23/24 (-AAGTTGG), IVS-I-110 (G→A), IVS-I-5 (G→C), IVS-II-745 (C→G), IVS-I-2 (T→C), FSC 8 (-AA), IVS-I,3'-end (-25 bp), IVS-I-1 (G→A), FSC 36/37 (-T), IVS-I-6 (T→C), FSC 5 (-CT), -28 (A→C), codon 37 (G→A), IVS-II-2,3 (+11/-2), -30 (T→A), and -88 (C→A). We have also revealed the existence of five new mutations from northern Iran, one of which (codon 37) is the first reported for Iran. Furthermore, the rate of unknown mutations is significantly reduced in our study (about 6%). These results could help with establishing a center for prenatal diagnosis, prevention, and control of thalassemia in the northern provinces of Iran. [ABSTRACT FROM AUTHOR]