Molecular diagnostics for haemoglobinopathies

Abstract

The globin gene mutations have been used as a prototype for the development of many techniques of mutation detection for > 30 years, and consequently there have been numerous PCR-based methods described that can be used for the molecular diagnosis of the haemoglobinopathies. This review describes the most commonly used current methods for the detection of each of the different types of thalassaemia mutation and abnormal haemoglobin, and reviews the most promising newer technology. In addition, it outlines the various diagnostic strategies commonly used for prenatal diagnosis by fetal DNA analysis and discusses the state of progress of the molecular analysis of cell-free DNA for non-invasive prenatal diagnosis. An understanding of which are the best current techniques for carrier detection and prenatal diagnosis of the full range of haemoglobinopathy mutations, and which of the newer, more complex technologies are being applied to the emerging approach of non-invasive prenatal diagnosis of beta thalassaemia and sickle cell disease. The haemoglobinopathies are a very heterogeneous group of genetic disorders with > 1300 different mutations described, from point mutations to large deletions and complex gene rearrangements. Despite the complexity of the disorders and the plethora of high-tech diagnostic methods developed, mutation screening and prenatal diagnosis are still carried out in many countries by simple and cheap in-house methods developed many years ago; however, the more advanced technologies may well play an essential role in the various approaches to non-invasive prenatal diagnosis haemoglobinopathies in the future.