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Previous Volume 351:1532-1538 October 7, 2004 Number 15 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Benz, E. J. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

SUMMARY

A baby girl presented with symptomatic sickle cell disease exacerbated by mild hypoxemia, despite a newborn-screening diagnosis of sickle cell trait. DNA sequencing of the globin gene revealed that her maternal globin allele was normal. Her paternal allele had not only the expected sickle-trait mutation, ^Glu6Val, but also a second, charge-neutral mutation, ^Leu68Phe. Analysis of the patient's hemoglobin revealed that the double-mutant protein, which we called "hemoglobin Jamaica Plain," had severely reduced oxygen affinity. Structural modeling suggested destabilization of the oxy conformation as a molecular mechanism for sickling in a heterozygote at an ambient partial pressure of oxygen.

Source Information

From the Division of Hematology–Oncology, Children's Hospital Boston (A.G., J.J.C., E.J.N.); the Dana–Farber Cancer Institute (J.J.C., E.J.N.); Harvard Medical School (J.J.C., E.J.N.); and the Department of Biology, Northeastern University (Y.Z., J.M.M.) — all in Boston; and Rockefeller University, New York (A.P.).

Address reprint requests to Dr. Neufeld at the Division of Hematology–Oncology, Children's Hospital Boston, Karp 8210, 300 Longwood Ave., Boston, MA 02115, or at ellis.neufeld{at}childrens.harvard.edu.

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