Severe factor XI deficiency caused by compound heterozygosity for the typeIII mutation and a novel insertion in exon 9 (codons 324/325+G)

We investigated a 42-year-old Caucasian woman with severe factor XI deficie ncy and her family members. Restriction enzyme analysis and DNA sequencing revealed compound heterozygosity in the patient for the known type III muta tion, which is a Phe283Leu amino acid substitution in the fourth apple doma in causing impaired dimerization and secretion, and for a novel frameshift mutation in exon 9 (codons 324/325 +G), leading to premature termination wi th lack of parts of the fourth apple domain and the downstream serine prote ase domain.