S. Koseki et al., Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation, BLOOD, 97(9), 2001, pp. 2667-2672
Two Japanese patients were newly diagnosed as having B subunit (XIIIB) defi
ciency of factor XIII (former type I deficiency). Both patients have a prev
iously described one-base deletion at the boundary between intron A/exon II
in the XIIIB gene, heterozygously or homozygously. A founder effect was pr
oposed for this mutation because 3 unrelated patients with XIIIB deficiency
also share 2 3'-polymorphisms. In one patient heterozygous for the above m
utation, a novel mutation was also identified: a deletion of guanosine in e
xon IX (delG) of the XIIIB gene. To understand the molecular and cellular p
athology of the delG mutation, expression studies were performed using a cu
ltured mammalian cell line. Pulse-chase experiments showed that a resultant
truncated XIIIB remained inside the cells and could not be secreted into t
he culture medium. Furthermore, immunocytochemical examinations by epifluor
escence, confocal, and electron microscopes indicated impaired intracellula
r transportation of the truncated XIIIB from the endoplasmic reticulum to t
he Golgi apparatus. No mutations in the gene for the A subunit (XIIIA) were
identified in this patient. Therefore, secretion of the truncated XIIIB mu
st also be impaired in vivo, leading to a secondary XIIIA deficiency. These
results support a previous conclusion that genetic defects of XIIIB are th
e basis for the former type I factor XIII deficiency. (Blood, 2001;97:2667-
2672) (C) 2001 by The American Society of Hematology.