Advances in Human Genetics by John B. Graham, Emily S. Barrow, Howard M. Reisner (auth.),

Advances in Human Genetics by John B. Graham, Emily S. Barrow, Howard M. Reisner (auth.),

By John B. Graham, Emily S. Barrow, Howard M. Reisner (auth.), Harry Harris, Kurt Hirschhorn (eds.)

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Shapiro and McCord, 1978). One patient with complete and singular absence of prothrombin for 2 weeks described by Karpatkin et al. (1962) would have died had it not been for daily transfusions. Complete lack of F. VII, IX, or X activity, on the other hand, is common in individuals with severe disease. Although the relationship of 26 John B. Graham et a/. symptoms to the degree of deficiency of a specific factor is complex and controversial, levels of activity above 20-25% of normal are generally not associated with excessive bleeding (S.

IX:C activity difficult to interpret in contaminated fetal samples. , 1979). It should be emphasized that the CRM status of a kindred must be determined before fetoscopic diagnosis of hemophilia B is contemplated. IX:Ag levels in the 20% of kindred who are CRM+ could lead to tragic results. Discussion of molecular variants of the vitamin K-dependent factors were forced until recently to ignore the 50-65% CRM - variants in whom no detectable protein is synthesized. IX. Similar rearrangements were not observed in the CRM - patients who did not develop inhibitors.

The lack of kringle sequences in Fs. , 1979). Factor VII has not yet been sequenced in this region. The Activation Peptide The third domain of the vitamin K-dependent serine proteases is the activation peptide, which may be cleaved from the zymogen during ac- Chapter 1: The Genetics of Blood Coagulation 19 tivation. This region differs in sequence and mass among the various vitamin K-dependent factors, but it is hydrophilic and acidic in all. X (X, and X2 ) differ by a single amino acid in this region (Jackson and Nemerson, 1980).

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