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Gaining ground on sickle cell disease
Date:7/15/2008

Although sickle cell disease is a single-gene disorder, its symptoms are highly variable. In a study published online July 14 by the Proceedings of the National Academy of Sciences, scientists at Children's Hospital Boston and the Dana Farber Cancer Institute (DFCI), in collaboration with the Broad Institute of MIT and Harvard, report five gene variants that could potentially be helpful in predicting sickle cell disease severity, perhaps even leading to better treatment approaches in the future.

The gene variants influence blood levels of fetal hemoglobin (HbF), which are known to affect symptom severity in sickle cell diseasewith some patients experiencing frequent, severe pain crises and organ damage, while others are scarcely aware of their disease.

"Our study is a first step towards a better understanding of fetal hemoglobin regulation in patients with sickle cell disease," says Guillaume Lettre, PhD, of the Broad Institute and Children's Hospital Boston, and co-first author on the paper. "But further validation experiments are needed before these findings can become useful in the clinic."

"Eventually, understanding the factors giving rise to heterogeneity in HbF levels might allow us to take severely affected patients and make them more like those with more benign symptoms," adds Vijay Sankaran, co-first author on the paper with Lettre and an MD-PhD student in the laboratory of Stuart Orkin, MD. (Orkin is chair of pediatric oncology at DFCI and a Howard Hughes Medical Institute investigator at Children's.)

In sickle cell disease, a single genetic mutation results in the production of an abnormal type of hemoglobin, the main component of red blood cells. The abnormal hemoglobin molecules tend to form long chains, causing red blood cells to become stiff and sickle-shaped. The distorted cells have difficulty passing through blood vessels and can block the smaller vessels, resulting in severe pain and eventual orga
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Contact: Bess Andrews
Elizabeth.Andrews@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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