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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2667-2672
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Truncated mutant B subunit for factor XIII causes its
deficiency due to impaired intracellular transportation
Shiori Koseki,
Masayoshi Souri,
Shinichiro Koga,
Mitsunori Yamakawa,
Tsutomu Shichishima,
Yukio Maruyama,
Fumio Yanai, and
Akitada Ichinose
From the Department of Molecular
Patho-Biochemistry and Patho-Biology, Department of Pathology, Yamagata
University School of Medicine, Japan; Department of Internal Medicine
I, Fukushima Prefectural Medical College, Japan; and Department of
Pediatrics, Fukuoka University School of Medicine, Japan.
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.
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