Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation.
Two Japanese patients were newly diagnosed as having B subunit (XIIIB) deficiency of factor XIII (former type I deficiency). Both patients have a previously described one-base deletion at the boundary between intron A/exon II in the XIIIB gene, heterozygously or homozygously. A founder effect was proposed for this mutation because 3 unrelated patients with XIIIB deficiency also share 2 3'-polymorphisms. In one patient heterozygous for the above mutation, a novel mutation was also identified: a deletion of guanosine in exon IX (delG) of the XIIIB gene. To understand the molecular and cellular pathology of the delG mutation, expression studies were performed using a cultured mammalian cell line. Pulse-chase experiments showed that a resultant truncated XIIIB remained inside the cells and could not be secreted into the culture medium. Furthermore, immunocytochemical examinations by epifluorescence, confocal, and electron microscopes indicated impaired intracellular transportation of the truncated XIIIB from the endoplasmic reticulum to the Golgi apparatus. No mutations in the gene for the A subunit (XIIIA) were identified in this patient. Therefore, secretion of the truncated XIIIB must also be impaired in vivo, leading to a secondary XIIIA deficiency. These results support a previous conclusion that genetic defects of XIIIB are the basis for the former type I factor XIII deficiency.
Koseki
S
S
Department of Molecular Patho-Biochemistry and Patho-Biology, Department of Pathology, Yamagata University School of Medicine, Japan.
Souri
M
M
Koga
S
S
Yamakawa
M
M
Shichishima
T
T
Maruyama
Y
Y
Yanai
F
F
Ichinose
A
A
Shitishima
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D005176:Factor XIII / Q000235:genetics* / Q000378:metabolism; D005177:Factor XIII Deficiency / Q000097:blood / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation
D005176:Factor XIII