**Core Concept:** Beta-thalassemia is a group of inherited blood disorders characterized by reduced or absent synthesis of beta-globin chains. HbA2 is a type of hemoglobin found in adults and is elevated in beta-thalassemia. The risk of having a child with beta-thalassemia major depends on the HbA2 levels of both parents.

**Why the Correct Answer is Right:** In beta-thalassemia, the risk of having a child with beta-thalassemia major depends on the degree of beta-thalassemia trait in both parents. If one parent is homozygous for beta-thalassemia (HbA2 level <2.5%) and the other is heterozygous (HbA2 level between 2.5-8%), the child has a 25% chance of being homozygous (beta-thalassemia major), a 50% chance of being heterozygous, and a 25% chance of being normal. **Why Each Wrong Option is Incorrect:** A. Reduced HbA2 levels indicate beta-thalassemia minor, not major. Beta-thalassemia major requires a higher HbA2 level (usually <2.5%). B. Although the wife has a lower HbA2 level, the couple has not yet reached the required criteria for beta-thalassemia major in the offspring. C. The higher HbA2 level in the husband does not negate the risk for beta-thalassemia major in their child. Both parents need to meet the criteria for beta-thalassemia trait to increase the risk for beta-thalassemia major in their child. D. The couple's HbA2 levels do not indicate their child's risk for beta-thalassemia major. The risk depends on the parents' genotype (genetic make-up) rather than their phenotype (observable characteristics). **Clinical Pearl:** Genetic counseling is essential for couples with a family history of inherited disorders like beta-thalassemia to understand their risk of having a child with severe anemia and other complications. Genetic counseling can guide them on prenatal diagnosis options like chorionic villus sampling (CVS) or amniocentesis.