Screening and genetic diagnosis of haemoglobin disorders

Abstract 

The inherited haemoglobinopathies are large group of disorders that include the thalassaemias and sickle cell disease. Carrier detection methods must be able to detect α-, β- and δβ-thalassaemias, HPFH disorders and haemoglobin variants. Carrier diagnosis involves the accurate measurement of MCH, MCV, Hb A₂ and Hb F values in combination with an understanding of the haematological characteristics of the different types of thalassaemia genes and their interactions. The majority of the common thalassaemia mutations and abnormal haemoglobins can be identified by PCR-based techniques. The main applications of molecular analysis for carrier diagnosis are: the analysis of α-thalassaemia mutations by gap-PCR to discriminate between heterozygous α-thalassaemia and homozygous α-thalassaemia; the identification of β-thalassaemia mutations for patients requiring prenatal diagnosis and for the prediction of the severity of the clinical phenotype of homozygous β-thalassaemia; to discriminate between δβ-thalassaemia and HPFH deletions by gap-PCR.

Keywords:  haemoglobinopathies, thalassaemia, carrier screening, mutation analysis