MOLECULAR DIAGNOSIS AND CARRIER SCREENING FOR BETA-THALASSEMIA

Thalassemias are common autosomal recessive disorders especially in po pulations of Mediterranean, Middle Eastern, and Far Eastern descent. R elatively high incidence is also observed in people of Asian Indian or igin but the incidence is more limited in those of African descent. be ta Thalassemias are heterogeneous at the molecular level, with more th an 150 different molecular defects identified to date. Despite this he terogeneity, each at-risk population has its own spectrum of common mu tations, usually from 5 to 10, a finding that simplifies mutation anal ysis. Homozygosity for beta thalassemias usually results in transfusio n-dependent thalassemia major and, rarely, in mild non-transfusion-dep endent conditions. Molecular diagnosis may be used to define genotypes associated with mild forms. Advances in carrier diagnosis using hemat ologic analysis followed by mutation analysis have made possible the p opulation screening of women al childbearing age and prenatal diagnosi s. This approach in combination with nondirective genetic counseling h as resulted in a consistent decline of the birth of affected homozygot es in several Mediterranean at-risk populations, as well as knowledge of the risks of being a carrier. Molecular diagnosis of homozygotes an d identification of carriers of beta thalassemia may lead to improved clinical management of patients with the disorder and prevention of th e birth of affected homozygotes.