Carrier Identification

p-Thalassemia carriers are identified by analysis of red blood cell indices, which show microcytosis and reduced MCH and Hb analysis, which displays high HbA2 (>3.5%). Pitfalls in carrier identification may result from several molecular mechanisms. Coinheritance of a-thal-assemia (two a-globin gene deletions or point mutations of the major a2 globin gene in p°-thalassemia, or even a single a-globin gene deletion in p+-thalassemia) may normalize the red blood cell indices of the p-thalassemia carrier. Nevertheless, the HbA2 concentration remains in the p-thalassemia carrier range and therefore has diagnostic value. Coinheritance of 8-thalassemia, which reduces the increased HbA2 levels typical of the p-thalassemia carrier state to normal, may cause confusion with the a-thalassemia carrier state. Differentiation of the double heterozygote state for 8- and p-thalassemia from the a-thalassemia heterozygote may be accomplished by globin chain synthesis analysis or globin gene analysis. Heterozygotes for mild p-thalassemia mutations (p+ IVS-I nt 6 mutation, gdp-, and 8p-thalassemia) may have normal HbA2 levels. However, 8p-thalassemias are characterized by high HbF levels.[1,11]

Based on these features, screening for p-thalassemia should be carried out by red cell indices analysis, Hb electrophoresis, and HbA2 quantitation. Molecular genetic testing to identify the p gene mutation is usually performed in the couples at risk for p-thalassemia and when the hematologic tests are not conclusive (i.e., borderline HbA2, microcytosis with normal A2 and F and normal iron, increased HbF). In some cases, molecular diagnosis may be helpful in patients to predict the clinical severity. Mutations are detected by several PCR-based procedures, such as reverse dot blot analysis or primer specific amplification using probes or primers complementary to the most common mutations present in the population or denaturing highperformance liquid chromatography. Sequence analysis is used if the previous methods fail to detect the mutation. Because of the high carrier rate, population screening is ongoing in several populations at risk (Sardinians, Continental Italians, Greeks, Cypriots) in Mediterranean area. In these populations, screening in combination with prenatal diagnosis has led to a marked reduction of the birth rate of homozygous p-thalassemia.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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