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 adults, to being relatively well even until old age. Increasing numbers of genetic loci have now been identified that can modulate sickle cell disease phenotype, from nucleotide motifs within the beta-globin gene cluster, to genes located on different chromosomes. With recent success of the human genome project, it is anticipated that many more genetic modifiers of sickle cell disease will be discovered that can lead to the development of more effective therapeutic approaches. The multigenic origin of the variable phenotype in sickle cell disease will serve as a paradigm for the study of variation in phenotypes of all single gene disorders in man.
Chui
D H
DH
Department of Pathology and Molecular Medicine, McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada. chuid@mcmaster.ca
Dover
G J
GJ
D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D016208:Databases, Factual; D005786:Gene Expression Regulation / Q000235:genetics; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic
D005914:Globins