Faculty Collaboration Database

ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood 1999 Apr 01;93(7):2261-6

Date

03/26/1999

Pubmed ID

10090935

Scopus ID

2-s2.0-0033120795 (requires institutional sign-in at Scopus site)   71 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.

Author List

Nichols WC, Terry VH, Wheatley MA, Yang A, Zivelin A, Ciavarella N, Stefanile C, Matsushita T, Saito H, de Bosch NB, Ruiz-Saez A, Torres A, Thompson AR, Feinstein DI, White GC, Negrier C, Vinciguerra C, Aktan M, Kaufman RJ, Ginsburg D, Seligsohn U

Author

Gilbert C. White MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Chromosomes, Bacterial
Cloning, Molecular
DNA Mutational Analysis
Exons
Factor V Deficiency
Female
Genes
Genes, Recessive
Genetic Heterogeneity
Genetic Linkage
Genotype
Haplotypes
Hemophilia A
Humans
Introns
Jews
Male
Mannose-Binding Lectins
Membrane Proteins
Mutation
Pedigree
Point Mutation
Polymerase Chain Reaction
Sequence Deletion