Sickle cell disease: no longer a single gene disorder

Patients who are homozygous for the sickle hemoglobin mutation can present with remarkably different clinical courses, varying from death in childhood , to recurrent painful vasoocclusive crises and multiple organ damage in ad ults, to being relatively well even until old age. Increasing numbers of ge netic loci have now been identified that can modulate sickle cell disease p henotype, from nucleotide motifs within the beta -globin gene cluster, to g enes located on different chromosomes. With recent success of the human gen ome project, it is anticipated that many more genetic modifiers of sickle c ell disease will be discovered that can lead to the development of more eff ective therapeutic approaches. The multigenic origin of the variable phenot ype in sickle cell disease will serve as a paradigm for the study of variat ion in phenotypes of all single gene disorders in man, (C) 2001 Lippincott Williams & Wilkins, Inc.