Screening extended families for genetic hemoglobin disorders in Pakistan

Background: We have investigated a strategy for identifying and counseling carriers of recessively inherited disorders in developing countries where consanguineous marriage is common. In such communities, gene variants are trapped within extended families, so that an affected child is a marker of a group at high genetic risk. Methods: Fifteen large Pakistani families, 10 with a history of a hemoglobin disorder and 5 without any such history (controls), were screened for (beta)-thalassemia and abnormal hemoglobins. All carriers and married couples consisting of two carriers received counseling, and eight families have been followed for two years. Results: In the control families, no carrier was found among 397 members tested. In the 10 families with an index case, 183 of 591 persons tested (31 percent) were carriers; carriers had a 25 percent risk of being in a marriage at risk for producing an affected child, and 17 of 214 married couples (8 percent) consisted of two carriers. No couple at risk was identified among 350 randomly selected pregnant women and their partners. All carriers reported that they have used the information provided in the testing and counseling process: carriers married to carriers with two or more healthy children have avoided further pregnancy, and most such couples with one or no healthy children have used prenatal diagnosis. Seven of eight new marriages and engagements are known not to be at risk. Conclusions: Testing of extended families is a feasible way of deploying DNA-based genetic screening in communities in which consanguineous marriage is common.