Prothrombin Carora: hypoprothrombinaemia caused by substitution of Tyr-44 by Cys

Two members of a family from Carora, Venezuela, were found to have prothrom bin activity levels at 4% of normal and undetectable antigen levels. All ex ons of the prothrombin gene from the proband were sequenced and a mutation at nucleotide 1305 was identified that would result in the substitution of Cys for Tyr at residue 44. Residue 44 is present in the aromatic stack regi on of the protein. Substitution of a Cys in this region would result in an abnormal folding of the protein which could be the cause for the observed l ack of secretion of the abnormal prothrombin.