A NOVEL MISSENSE MUTATION IN 2 FAMILIES WITH CONGENITAL PLASMINOGEN DEFICIENCY - IDENTIFICATION OF AN ALA(675) TO THR(675) SUBSTITUTION

We used a polymerase chain reaction (PCR) strategy and restriction fra gment polymorphism analysis to evaluate all 19 exons of the plasminoge n (PLG) gene in a Japanese patient with congenital PLG deficiency and her family members (family C). Sequence analysis following amplificati on of each exon and its flanking regions showed a single G to A transi tion in exon 17, resulting in the conversion of an Ala(675) codon (GCT ) to Thr(675) codon (ACT). Since this mutation generates a new Mne III site, the Mne III digestion patterns of the PCR-amplified exon 17 fra gments from each family member were analyzed. In all cases, the patter ns correlated with the activities and antigen levels of plasma PLG in those members. The identical G to A transition in the same codon of ex on 17 was detected by a Mae III digestion experiment in another proban d and her family members with congenital PLG deficiency (family K). Fu rthermore, 20 normal individuals examined had no Mne III restriction s ite at this location, We conclude that a G to A transition in exon 17 is responsible for the congenital PLG deficiency inherited in these tw o Japanese families.