Factor XIII(A) subunit deficiency due to a homozygous 13-base pair deletion in exon 3 of the A subunit gene.

We investigated the molecular basis of factor XIII(A) subunit deficiency in a Greek family. Each of the 15 exons of the A subunit gene were individually amplified by polymerase chain reaction, using previously reported oligoprimers. The proband with severe deficiency was found to have a homozygous 13-base pair deletion in the 3' half of exon 3. The deleted sequence, extending from codons 82-86, results in a frameshift and generates a downstream termination codon in exon 4. Single strand conformation polymorphism (SSCP) analysis detected no additional mutations in the coding or consensus splice sequences of the A subunit gene. Both parents of the proband were heterozygous for the defect. Only one previous microdeletion (AG dinucleotide) has been reported in the A subunit gene, and was located at the intron B-exon 3 boundary. Further studies are necessary to determine whether this region of the gene is a "hot spot" for microdeletion mutations.