Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor

Harold R. Roberts; James E. Grizzle; William D. McLester; George D. Penick

doi:10.1172/JCI105732

^{Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

^{Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

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^{Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

^{Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

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^{Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

^{Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

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^{Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

^{Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina}

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Published in Volume 47, Issue 2 on February 1, 1968
J Clin Invest. 1968;47(2):360–365. https://doi.org/10.1172/JCI105732.
© 1968 The American Society for Clinical Investigation

Published February 1, 1968 - Version history

Hemophilia B can be divided into at least two mutant forms different from the mild, moderate, and severe categories previously described. In about 90% of hemophilia B patients, PTC-inhibitor-neutralizing activity is reduced in proportion to PTC clotting activity. In about 10% of the patients, PTC-inhibitor-neutralizing activity is fully effective, whereas PTC clotting activity is reduced. Extensive pedigree studies indicate that the presence or absence of inhibitor-neutralizing activity is genetically determined. It is suggested that those hemophilia B mutants with decreased inhibitor-neutralizing material produce decreased amounts of PTC-protein. It is further suggested that those with normal levels of inhibitor-neutralizing material produce normal amounts of PTC-protein, which is structurally altered so as to lose procoagulant activity but which retains inhibitor-neutralizing activity. The latter group may be analogous to CRM⁺ mutants described in bacteria and Neurospora.