학술논문
Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1or MCFD2
Document Type
Article
Author
Zhang, Bin; McGee, Beth; Yamaoka, Jennifer S.; Guglielmone, Hugo; Downes, Katharine A.; Minoldo, Salvador; Jarchum, Gustavo; Peyvandi, Flora; de Bosch, Norma B.; Ruiz-Saez, Arlette; Chatelain, Bernard; Olpinski, Marian; Bockenstedt, Paula; Sperl, Wolfgang; Kaufman, Randal J.; Nichols, William C.; Tuddenham, Edward G.D.; Ginsburg, David
Source
Blood; March 2006, Vol. 107 Issue: 5 p1903-1907, 5p
Subject
Language
ISSN
00064971; 15280020
Abstract
Mutations in LMAN1 (ERGIC-53)or MCFD2cause combined deficiency of factor V and factor VIII (F5F8D). LMAN1 and MCFD2 form a protein complex that functions as a cargo receptor ferrying FV and FVIII from the endoplasmic reticulum to the Golgi. In this study, we analyzed 10 previously reported and 10 new F5F8D families. Mutations in the LMAN1or MCFD2genes accounted for 15 of these families, including 3 alleles resulting in no LMAN1mRNA accumulation. Combined with our previous reports, we have identified LMAN1or MCFD2mutations as the causes of F5F8D in 71 of 76 families. Among the 5 families in which no mutations were identified, 3 were due to misdiagnosis, with the remaining 2 likely carrying LMAN1or MCFD2mutations that were missed by direct sequencing. Our results suggest that mutations in LMAN1and MCFD2may account for all cases of F5F8D. Immunoprecipitation and Western blot analysis detected a low level of LMAN1-MCFD2 complex in lymphoblasts derived from patients with missense mutations in LMAN1 (C475R) or MCFD2 (I136T), suggesting that complete loss of the complex may not be required for clinically significant reduction in FV and FVIII.