PMID- 10090934
OWN - NLM
STAT- MEDLINE
DCOM- 19990419
LR  - 20170922
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 7
DP  - 1999 Apr 1
TI  - Molecular analysis of the ERGIC-53 gene in 35 families with combined factor
      V-factor VIII deficiency.
PG  - 2253-60
AB  - Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive
      coagulation disorder in which the levels of both coagulation factors V and VIII
      are diminished. The F5F8D locus was previously mapped to a 1-cM interval on
      chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were
      recently found to be associated with the coagulation defect in nine Jewish
      families. We performed single-strand conformation and sequence analysis of the
      ERGIC-53 gene in 35 F5F8D families of different ethnic origins. We identified 13 
      distinct mutations accounting for 52 of 70 mutant alleles. These were 3 splice
      site mutations, 6 insertions and deletions resulting in translational
      frameshifts, 3 nonsense codons, and elimination of the translation initiation
      codon. These mutations are predicted to result in synthesis of either a truncated
      protein product or no protein at all. This study revealed that F5F8D shows
      extensive allelic heterogeneity and all ERGIC-53 mutations resulting in F5F8D are
      "null." Approximately 26% of the mutations have not been identified, suggesting
      that lesions in regulatory elements or severe abnormalities within the introns
      may be responsible for the disease in these individuals. In two such families,
      ERGIC-53 protein was detectable at normal levels in patients' lymphocytes,
      raising the further possibility of defects at other genetic loci.
FAU - Neerman-Arbez, M
AU  - Neerman-Arbez M
AD  - Department of Genetics and Microbiology, Division of Medical Genetics, University
      of Geneva Medical School, Switzerland.
FAU - Johnson, K M
AU  - Johnson KM
FAU - Morris, M A
AU  - Morris MA
FAU - McVey, J H
AU  - McVey JH
FAU - Peyvandi, F
AU  - Peyvandi F
FAU - Nichols, W C
AU  - Nichols WC
FAU - Ginsburg, D
AU  - Ginsburg D
FAU - Rossier, C
AU  - Rossier C
FAU - Antonarakis, S E
AU  - Antonarakis SE
FAU - Tuddenham, E G
AU  - Tuddenham EG
LA  - eng
GR  - MC_U120074259/Medical Research Council/United Kingdom
GR  - HL38165/HL/NHLBI NIH HHS/United States
GR  - P01-HL57346/HL/NHLBI NIH HHS/United States
GR  - R01-HL39693/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Codon)
RN  - 0 (LMAN1 protein, human)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Membrane Proteins)
SB  - AIM
SB  - IM
MH  - Algeria/ethnology
MH  - Alleles
MH  - China/ethnology
MH  - Codon/genetics
MH  - Consanguinity
MH  - DNA Mutational Analysis
MH  - Ethnic Groups/genetics
MH  - Factor V Deficiency/complications/ethnology/*genetics
MH  - Female
MH  - Genes, Recessive
MH  - Haplotypes
MH  - Hemophilia A/complications/ethnology/*genetics
MH  - Humans
MH  - Iran/ethnology
MH  - Italy/ethnology
MH  - Jews/genetics
MH  - Male
MH  - *Mannose-Binding Lectins
MH  - Membrane Proteins/deficiency/*genetics
MH  - *Mutation
MH  - Pakistan/ethnology
MH  - Polymorphism, Single-Stranded Conformational
MH  - South Africa/ethnology
MH  - United Kingdom/ethnology
EDAT- 1999/03/26 00:00
MHDA- 1999/03/26 00:01
CRDT- 1999/03/26 00:00
PHST- 1999/03/26 00:00 [pubmed]
PHST- 1999/03/26 00:01 [medline]
PHST- 1999/03/26 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Apr 1;93(7):2253-60.