Molecular diagnosis and carrier screening for beta thalassemia
A. Cao, L. Saba, R. Galanello and M. C. Rosatelli
Istituto di Clinica e Biologia dell'Eta Evolutiva-Universita degli Studi di Cagliari, Italy. acao@hcweb.unica.it
Thalassemias are common autosomal recessive disorders especially in
populations of Mediterranean, Middle Eastern, and Far Eastern descent.
Relatively high incidence is also observed in people of Asian Indian origin
but the incidence is more limited in those of African descent. Beta
Thalassemias are heterogeneous at the molecular level, with more than 150
different molecular defects identified to date. Despite this heterogeneity,
each at-risk population has its own spectrum of common mutations, usually
from 5 to 10, a finding that simplifies mutation analysis. Homozygosity for
beta thalassemias usually results in transfusion-dependent thalassemia
major and, rarely, in mild non-transfusion-dependent conditions. Molecular
diagnosis may be used to define genotypes associated with mild forms.
Advances in carrier diagnosis using hematologic analysis followed by
mutation analysis have made possible the population screening of women at
childbearing age and prenatal diagnosis. This approach in combination with
nondirective genetic counseling has resulted in a consistent decline of the
birth of affected homozygotes in several Mediterranean at-risk populations,
as well as knowledge of the risks of being a carrier. Molecular diagnosis
of homozygotes and identification of carriers of beta thalassemia may lead
to improved clinical management of patients with the disorder and
prevention of the birth of affected homozygotes.
