الفهرس 
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Abstract
β-thalassemias represent a group of hereditary blood disorders characterized by anomalies in the synthesis of the β chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. β-thalassemia is common in Egypt and clinically has a wide range of severity.
More than 200 mutations have been reported so far, the large majority are point mutations in functionally important regions of the β-globin gene. Deletions of the β-globin gene are also been reported but are uncommon. In each population only a few common mutations in the β-globin have been found to be responsible for β-thalassemia, which indicate population differences.
The aim of the work was to detect the common mutations among Egyptian patients with β-thalassemia, and to diagnose the carriers among their first degree relatives to provide accurate genetic counseling.
The study included fifty-one patients described earlier as β-thalassemic patients, and fifty-five members of their relatives (parents or sibs).
All patients and their relatives were subjected to the following:
• Full history taking
• Clinical examination
• Pedigree construction and analysis
• Laboratory investigations which included complete blood picture and hemoglobin electrophoresis
• Serum ferritin testing for the patients only
• Molecular analysis for the detection of the β-globin mutations only in the patients, by StripAssay method.
The results obtained were tabulated and statistically analyzed using MedCalc Software. The results were diagrammatically represented. They were considered significant if (p<0.05).
The patients were 27 males (52.94%) and 24 females (47.06%), with age ranging between 3-40 years, mean of 16.52±7.05 years. The relatives included 15 males (27.27%) and 40 females (72.72%), with age ranging between 2-63 years, mean of 39.36±14.02 years.
Clinical data of the patients revealed splenomegaly in 20 patients (39.22%), 13 patients (25.49%) were splenectomized and intact spleen in the other 18 patients (35.29%). It also revealed 45 patients (88.24%) were blood-transfusion dependent and the other 6 patients (11.76%) were blood-transfusion independent.
The data showed that 24 patients (47.06%) were born for consanguineous parents, where 27 patients (52.94%) were born for non-consanguineous parents.
The mean HbA level in the patients was 81.48±20.17% and the median was 89. 5%, while in their relatives the mean was 95.7±4.26% and the median was 95.97%. The mean in the patients is lower than that of the relatives.
The mean HbF level in the patients was 14.63±19.82% and the median was 7.5%, while in their relatives the mean was 0.56±3.99% and the median was 0%. The mean in the patients is higher than that of the relatives.
The mean HbA2 level in the patients was 3.87±1.98% and the median was 3.2%, while in their relatives the mean was 3.73±1.28% and the median was 4.03%. The mean in the patients is slightly higher than that of the relatives.
The mean Hb concentration in the patients was 8.13±1.65 g/dL and the median was 8 g/dL, while in their relatives the mean was 11.22±1.42 g/dL, and the median was 11 g/dL. The mean in the patients is lower than that of the relatives.
The mean RBC count in the patients was 3.66±0.95x1012/L and the median was 3.64x1012/L, while in their relatives the mean was 5.28±0.53x1012/L, and the median was 5.33x1012/L. The mean in the patients is lower than that of the relatives.
The mean HCT level in the patients was 25.25±5.19% and the median was 24.8%, while in their relatives the mean was 34.71±3.57%, and the median was 34.5%. The mean in the patients is lower than that of the relatives.
The mean MCV level in the patients was 70.38±11.66 fL and the median was 71.1 fL, while in their relatives the mean was 66.46±8.33 fL, and the median was 65 fL. The mean in the patients is higher than that of the relatives.
The mean MCH level in the patients was 22.93±4.29 pg and the median was 23.5 pg, while in their relatives the mean was 21.57±3.46 pg, and the median was 20.5 pg. The mean in the patients is slightly higher than that of the relatives.
The mean MCHC level in the patients was 32.5±2.08 g/dL and the median was 32.8 g/dL, while in their relatives the mean was 32.3±1.51 g/dL, and the median was 32.2 g/dL. The mean in the patients is almost equal to that of the relatives.
The mean WBC count in the patients was 14.58±17.78x109/L and the median was 7.87x109/L, while in their relatives the mean was 7.2±2.55x109/L, and the median was 6.87x109/L. The mean in the patients is higher than that of the relatives.
The mean platelet count in the patients was 339.58±188.71x109/L and the median was 300x109/L, while in their relatives the mean was 279.85±75.14x109/L, and the median was 276x109/L. The mean in the patients is higher than that of the relatives.
The mean serum ferritin level in the patients was 1632.58±1803.24 ng/mL and the median was 1400 ng/mL.
Hematological and family studies of the relatives showed that 42 individuals (76.36%) were an obligate carrier, 7 individuals (12.74%) were carriers and the other 6 relatives (10.9%) were non-carriers.
Molecular analysis of the β-globin gene mutations identified ten different mutations. These mutations were: IVS-I-6 in nineteen alleles (32. 2%), IVS-I-110 in thirteen alleles (22.03%), IVS-I-1 in seven alleles (11.86%), IVS-II-848 in six alleles (10.16%), IVS -II-745 in four alleles (6.77%), -87 in three alleles (5.08%), Codon 5 in three alleles (5.08%), Codon 39 in two alleles (3.38%), Codon 27 in one allele (1.69%) and Codon 8 in one allele (1.69%).
This work described four patients (8.51%) with β-thalassemia major, thirty three patients (70.21%) with β-thalassemia intermedia, nine patients (19.14%) with β-thalassemia minor, and one patient (2.12%) was identified as normal.
We could not find any genotype-phenotype correlation among the studied β-thalassemia patients.