Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation

Citation
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
Citations number
20
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
97
Issue
9
Year of publication
2001
Pages
2667 - 2672
Database
ISI
SICI code
0006-4971(20010501)97:9<2667:TMBSFF>2.0.ZU;2-T
Abstract
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.