GENETIC-ANALYSIS IN JAPANESE KINDREDS OF CONGENITAL TYPE-I ANTITHROMBIN DEFICIENCY CAUSING THROMBOSIS

We have identified two novel minor deletions (case 1; -TA or -AT at nu cleotide 9831-3 in exon 5 and case 2: -A at nucleotide 7640-1 in exon 4), one novel nonsense mutation (case 3; TAT to TAA at nucleotide 7491 in exon 4), and one recurrent nonsense mutation (case 4; CGA to TGA a t nucleotide 5381 in exon 3A) in Japanease kindreds with congenital ty pe I antithrombin deficiency. The deletion detected in case 1 represen ted a symmetric element (CTCTGTCTC) and possessed a direct repeat (CTC TATGTCTC). The deletion in case 2 was recognized in a consensus sequen ce (TGAAT) and possessed a direct repeat (GATGAA). The nonsense mutati on in case 3 formed a palindrome (CCGTTAACGG) and that in case 4 was c aused by a CpG dinucleotide mutation. These results confirm that the m utations of congenital type I antithrombin deficiency are not random e vents but are influenced strongly by DNA sequences.