title: ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families.
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.
authors: Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, OH, USA.
authors: W C
authors: WC
authors: Nichols
authors: V H
authors: VH
authors: Terry
authors: M A
authors: MA
authors: Wheatley
authors: A
authors: A
authors: Yang
authors: A
authors: A
authors: Zivelin
authors: N
authors: N
authors: Ciavarella
authors: C
authors: C
authors: Stefanile
authors: T
authors: T
authors: Matsushita
authors: H
authors: H
authors: Saito
authors: N B
authors: NB
authors: de Bosch
authors: A
authors: A
authors: Ruiz-Saez
authors: A
authors: A
authors: Torres
authors: A R
authors: AR
authors: Thompson
authors: D I
authors: DI
authors: Feinstein
authors: G C
authors: GC
authors: White
authors: C
authors: C
authors: Negrier
authors: C
authors: C
authors: Vinciguerra
authors: M
authors: M
authors: Aktan
authors: R J
authors: RJ
authors: Kaufman
authors: D
authors: D
authors: Ginsburg
authors: U
authors: U
authors: Seligsohn
mesh_terms: D019943:Amino Acid Substitution; D002876:Chromosomes, Bacterial; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005166:Factor V Deficiency / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005796:Genes; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006467:Hemophilia A / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007585:Jews / Q000235:genetics; D008297:Male; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
chemical_list: C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins