Premium
Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies
Author(s) -
Patrinos George P.,
Kollia Panagoula,
Papadakis Manoussos N.
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20225
Subject(s) - biology , thalassemia , genetics , disease , genetic heterogeneity , prenatal diagnosis , genetic counseling , locus (genetics) , phenotype , hum , computational biology , bioinformatics , gene , medicine , fetus , pathology , pregnancy , art , performance art , art history
Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA sequence of the human α‐like ( HBZ , HBA2 , HBA1 , and HBQ1 ) and β‐like ( HBE1 , HBG2 , HBG1 , HBD , and HBB ) globin genes are mainly responsible for the observed clinical heterogeneity. These mutations, together with detailed information about the resulting phenotype, are documented in the globin locus‐specific HbVar database. Family studies and comprehensive hematological analyses provide useful insights for accurately diagnosing thalassemia at the DNA level. For this purpose, numerous techniques can provide accurate, rapid, and cost‐effective identification of the underlying genetic defect in affected individuals. The aim of this article is to review the diverse methodological and technical platforms available for the molecular diagnosis of inherited disorders, using thalassemia and hemoglobinopathies as a model. This article also attempts to shed light on issues closely related to thalassemia diagnostics, such as prenatal and preimplantation genetic diagnoses and genetic counseling, for better‐quality disease management. Hum Mutat 26(5), 399–412, 2005. © 2005 Wiley‐Liss, Inc.