ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families

William C. Nichols, Valeri H. Terry, Matthew A. Wheatley, Angela Yang, Ariella Zivelin, Nicola Ciavarella, Caterina Stefanile, Tadashi Matsushita, Hidehiko Saito, Norma B. De Bosch, Arlette Ruiz-Saez, Argimiro Torres, Arthur R. Thompson, Donald I. Feinstein, Gilbert C. White, Claude Negrier, Christine Vinciguerra, Melih Aktan, Randal J. Kaufman, David Ginsburg*Uri Seligsohn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Combined factors V and VIII deficiency is an autosomal recessive bleeding disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% of normal. The disease gene was recently identified as the endoplasmic reticulum-Golgi intermediate compartment protein ERGIC-53 by positional cloning, with the detection of two founder mutations in 10 Jewish families. To identify mutations in additional families, the structure of the ERGIC-53 gene was determined by genomic polymerase chain reaction (PCR) and sequence analysis of bacterial artificial chromosome clones containing the ERGIC-53 gene. Nineteen additional families were analyzed by direct sequence analysis of the entire coding region and the intron/exon junctions. Seven novel mutations were identified in 10 families, with one additional family found to harbor one of the two previously described mutations. All of the identified mutations would be predicted to result in complete absence of functional ERGIC-53 protein. In 8 of 19 families, no mutation was identified. Genotyping data indicate that at least two of these families are not linked to the ERGIC-53 locus. Taken together, these results suggest that a significant subset of combined factors V and VIII deficiency is due to mutation in one or more additional genes.

Original languageEnglish
Pages (from-to)2261-2266
Number of pages6
JournalBlood
Volume93
Issue number7
StatePublished - 1 Apr 1999

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteP01HL057346

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