The molecular genetics of factor XI deficiency

Hereditary factor XI deficiency is characterised by a functional deficiency of factor XI and the absence of factor XI-related antigen in circulation. It occurs with a high frequency in the Ashkenazi Jewish population. Cloning of abnormal factor XI genes and studies on the molecular genetics of factor XI deficiency show that the cause for factor XI deficiency is heterogeneous. So far, two independent single base substitutions, one at the conserved intron donor consensus dinucleotide of intron N (type I) and a nonsense mutation at the codon for Glu117 (type II), have been identified. These two types of mutation together account for approximately half of the genetic changes in abnormal factor XI genes. At least one or more types of genetic change has yet to be defined. In the course of these studies, rapid methods that utilize the polymerase chain reaction and subsequent restriction endonuclease analysis have been developed.