title: Type I factor XIII deficiency is caused by a genetic defect of its b subunit: insertion of triplet AAC in exon III leads to premature termination in the second Sushi domain.
abstract: Factor XIII deficiency has been classified into two categories: type I deficiency, characterized by the lack of both the a and b subunits; and type II deficiency, characterized by the lack of the a subunit alone. To clarify the genetic bases of these diseases, previously reported cases of the type I deficiency were examined at the DNA level. DNA sequence analysis showed that a nucleotide triplet (AAC) was inserted within the codon for Tyr-80 in exon III of the gene for a female proband's b subunit, resulting in the creation of a stop codon. Restriction digestion of amplified DNAs confirmed that the proband and her sister were homozygotes, and their family members were heterozygotes of this mutant allele. A truncated protein composed of 79 amino acids could be synthesized by these homozygotes; however, such a protein would not be secreted or it would degrade quickly, because there were normal amounts of the mutant mRNA, but no b subunit was detected in these patients. The a subunit deficiency of these patients must be a secondary to the b subunit deficiency, as their gene for the a subunit was intact, and the a subunit in their platelets was present within normal levels.
authors.affiliation: Department of Molecular Patho-Biochemistry, Yamagata University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Izumi
authors.forename: T
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: A
authors.initials: A
authors.lastname: Tosetto
authors.forename: F
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: A
authors.initials: A
authors.lastname: Girolami
authors.forename: A
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017421:Sequence Analysis
chemical_list: D005176:Factor XIII