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November 1993

Sickle Cell Anemia: βs Gene Cluster Haplotypes as Genetic Markers for Severe Disease Expression

Author Affiliations

From the Division of Hematology, Department of Pediatrics (Dr Powars), and the Department of Pathology (Dr Hiti), University of Southern California, Los Angeles.

Am J Dis Child. 1993;147(11):1197-1202. doi:10.1001/archpedi.1993.02160350071011

• Identification of the βs gene cluster haplotype and α-gene status provides a useful tool for the detection of high-risk patients with sickle cell anemia. Analysis of the relationship of the long-term clinical course to the above parameters has revealed that those with the haplotype designated Senegal have decreased severity, those with the Benin haplotype have intermediate severity, and those with the Central African Republic (CAR) haplotype have the most severe clinical expression. Further modulation of the clinical course occurs with the coinheritance of α-thalassemia-2. In both Africa and the United States, the CAR βs haplotype increased the risk (relative risk, 2.25; 95% confidence interval, 1.41 to 3.87) of developing a complication and death at an early age. Detection of the CAR haplotype identifies the child with sickle cell anemia at risk for a rapid rate of progression of sickle-induced microvasculopathy, ultimately leading to irreversible organ damage during the first three decades of life. In patients with the CAR haplotype, potential curative therapy, such as bone marrow transplantation or gene insertion, should be seriously considered during childhood, before organ failure is clinically evident.

(AJDC. 1993;147:1197-1202)

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