We report a new homozygous CTG-->tCCG (Leu-->Pro) mutation at codon 354 in
the factor XIIIA gene of a patient suffering from FXIII deficiency. Leu354
lies in a pocket within the core domain of the FXIIIA molecule, with its si
de chain pointing into the structure of the barrel 1 domain. Replacement of
leucine with a proline residue gives rise to steric hindrance between the
proline ring and the surrounding residues, and rearrangement of these resid
ues would be necessary for proline to be accommodated at this position. Usi
ng PCR-RFLP, we have demonstrated the absence of this mutation from 220 nor
mal alleles. Together, these data suggest that Leu354Pro is likely to be th
e disease-causing mutation in this factor XIII deficient family.