Genotype/Phenotype Correlation of ß-Thalassemia in Syrian Patients: A Cross-Sectional Study.

ß-Thalassemia (ß-thal) is an inherited blood disorder caused by reduced or absent synthesis of ß-globin chains leading to imbalance of globin chain synthesis. ß0-Thalassemia (ß0-thal), refers to the complete absence of ß-globin chain production on the affected allele. ß+-Thalassemia (ß+-thal) refers to alleles with some residual production of ß-globin chain. We studied the correlation of genotype/phenotype of ß-thal disease in Syrian patients. A cross-sectional study was carried out on 260 patients with ß-thal. Genotyping was determined by a DNA sequencing technique. Routine investigations were performed to assess the complete blood count (CBC), serum ferritin, Hb A2 and Hb F levels. We found that the ß0/ß0 genotype was the most common in our patients followed by ß+/ß+ and ß0/ß+. Patients with ß0/ß0 received transfusions at an earlier age and more frequently when compared to those with ß0/ß+ and ß+/ß+ genotypes. Moreover, patients with ß0/ß0 had higher levels of Hb F and lower levels of Hb A2 compared to those with ß0/ß+ and ß+/ß+ genotypes. All patients with ß-thal intermedia (ß-TI) carry the ß+/ß+ genotype, while all patients with ß0/ß0 and ß0/ß+ genotypes presented with transfusion-dependent ß-thal major (ß-TM).

Molecular update of ß-thalassemia mutations in the Syrian population: identification of rare ß-thalassemia mutations.

ß-Thalassemia (ß-thal) is an autosomal recessive disorder characterized by variable degrees of anemia, bone marrow hyperplasia, splenomegaly, and complications related to the severity of the anemic state. The ß-thalassemias result from mutations in and around the ß-globin gene (HBB) located as a cluster on the short arm of chromosome 11. In Syria, ß-thal is highly prevalent. The main aim of this study was to identify the frequency of HBB mutations in 189 Syrian ß-thal patients and carriers of ß-thal. Out of the 189 patients and carriers recruited in this study, 181 patients had at least one HBB mutation and eight patients did not show any mutation. The 10 most frequent ones constituted 77.5% of all HBB mutations. These mutations in order of frequency were: IVS-I-110 (G > A) (17.0%), IVS-I-1 (G > A) (14.7%), codon 39 (C > T) (14.4%), IVS-II-1 (G > A) (9.8%), codon 8 (-AA) (6.2%), IVS-I-6 (T > C) (5.2%), IVS-I-5 (G > C) (4.9%), codon 5 (-C) (3.2%), IVS-I-5 (G > A) (3.2%) and codon 37 (G > A) (2.2%). Another 21 mutations were less frequent or sporadic. These results provide important tools for adapting a prenatal molecular diagnostic test for the Syrian population.

Geographical distribution of ß-globin gene mutations in Syria.

OBJECTIVES: ß-Thalassemia disease is caused by mutations in the ß-globin gene. This is considered as one of the common genetic disorders in Syria. The aim of this study was to identify the geographical distribution of the ß-thalassemia mutations in Syria. METHODS: ß-Globin gene mutations were characterized in 636 affected patients and 94 unrelated carriers using the amplification refractory mutations system-polymerase chain reaction technique and DNA sequencing. RESULTS: The study has revealed the presence of 38 ß-globin gene mutations responsible for ß-thalassemia in Syria. Important differences in regional distribution were observed. IVS-I.110 [G > A] (22.2%), IVS-I.1 [G > A] (17.8%), Cd 39 [C > T] (8.2%), IVS-II.1 [G > A] (7.6%), IVS-I.6 [T > C] (7.1%), Cd 8 [-AA] (6%), Cd 5 [-CT] (5.6%) and IVS-I.5 [G > C] (4.1%) were the eight predominant mutations found in our study. The coastal region had higher relative frequencies (37.9 and 22%) than other regions. A clear drift in the distribution of the third common Cd 39 [C > T] mutation in the northeast region (34.8%) to the northwest region (2.5%) was noted, while the IVS-I.5 [G > C] mutation has the highest prevalence in north regions. The IVS-I.6 [T > C] mutation had a distinct frequency in the middle region. Ten mutations -86 [C > G], -31 [A > G], -29 [A > G], 5'UTR; +22 [G > A], CAP + 1 [A > C], Codon 5/6 [-TG], IVS-I (-3) or codon 29 [C > T], IVS-I.2 [T > A], IVS-I.128 [T > G] and IVS-II.705 [T > G] were found in Syria for the first time. CONCLUSIONS: These data will significantly facilitate the population screening, genetic counseling and prenatal diagnosis in Syrian population.