Homozygous truncation of the fibrinogen Aα chain within the coiled coil causes congenital afibrinogenemia

The molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family, suffers from a moderate to severe bleeding disorder due to the total absence of any detectable fibrinogen. Dot blots of solubilized platelets r...

Full description

Saved in:
Bibliographic Details
Published inBlood Vol. 96; no. 2; pp. 773 - 775
Main Authors Fellowes, Andrew P., Brennan, Stephen O., Holme, Randi, Stormorken, Helge, Brosstad, Frank R., George, Peter M.
Format Journal Article
LanguageEnglish
Published 15.07.2000
Online AccessGet full text

Cover

Abstract The molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family, suffers from a moderate to severe bleeding disorder due to the total absence of any detectable fibrinogen. Dot blots of solubilized platelets revealed a small amount of γ chain but no A or Bβ chains, whereas no chains were detected in plasma dot blots. DNA sequencing of the A chain gene revealed a homozygous C→T transversion 557 nucleotides from the transcription initiation site. This nucleotide change predicts the nonsense mutation A 149 Arg (CGA)→stop (TGA). Early truncation of the A chain appears to result in defective assembly or secretion of fibrinogen, probably due to the removal of the C-terminal disulfide ring residues that are critically required for the formation of a stable 3-chained half molecule.
AbstractList The molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family, suffers from a moderate to severe bleeding disorder due to the total absence of any detectable fibrinogen. Dot blots of solubilized platelets revealed a small amount of γ chain but no A or Bβ chains, whereas no chains were detected in plasma dot blots. DNA sequencing of the A chain gene revealed a homozygous C→T transversion 557 nucleotides from the transcription initiation site. This nucleotide change predicts the nonsense mutation A 149 Arg (CGA)→stop (TGA). Early truncation of the A chain appears to result in defective assembly or secretion of fibrinogen, probably due to the removal of the C-terminal disulfide ring residues that are critically required for the formation of a stable 3-chained half molecule.
Author Stormorken, Helge
George, Peter M.
Brosstad, Frank R.
Fellowes, Andrew P.
Brennan, Stephen O.
Holme, Randi
Author_xml – sequence: 1
  givenname: Andrew P.
  surname: Fellowes
  fullname: Fellowes, Andrew P.
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
– sequence: 2
  givenname: Stephen O.
  surname: Brennan
  fullname: Brennan, Stephen O.
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
– sequence: 3
  givenname: Randi
  surname: Holme
  fullname: Holme, Randi
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
– sequence: 4
  givenname: Helge
  surname: Stormorken
  fullname: Stormorken, Helge
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
– sequence: 5
  givenname: Frank R.
  surname: Brosstad
  fullname: Brosstad, Frank R.
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
– sequence: 6
  givenname: Peter M.
  surname: George
  fullname: George, Peter M.
  organization: From the Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand; and the Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
BookMark eNpVkMtKAzEUhoNUsK2-Q1buZjy5zWUjlKJWKLhRtyHJJG3qNJHJFKlv5Yv4TJ1WQVwcvh_Of87im6BRiMEidE0gJ6SiN7qNsclf6yKneVmyHAh_g1IOcRhxhsZE0CoDoDBCYwAoMl6X5AJNUtrAUGZUjNFmEbfxc7-Ku4T7bheM6n0MODrcry12Xnc-xJUNePb9hc1a-YA_fL8ecNyb6FvbnICN2iWbhhyGuu9Vi9Xfud16dYnOnWqTvfrlFL3c3z3PF9ny6eFxPltmhpBCZLRUyjSudpzzutFaNYVwRVNqK7StNOGlggocJZQUDWeOCNBUaVETy8Cwmk3R7c9f08WUOuvke-e3qttLAvJoTp7MycGcpCdd_82xA550aoQ
CitedBy_id crossref_primary_10_1046_j_1365_2516_2002_00633_x
crossref_primary_10_1097_01_mbc_0000164434_51534_a8
crossref_primary_10_1046_j_1365_2141_2003_03985_x
crossref_primary_10_1046_j_1538_7836_2003_00425_x
crossref_primary_10_1097_MBC_0b013e3283256024
crossref_primary_10_1046_j_1538_7836_2003_00224_x
crossref_primary_10_1182_blood_V96_7_2496_h8002496_2496_2500
crossref_primary_10_1016_S0167_4838_01_00280_1
crossref_primary_10_1046_j_1468_0734_2001_00051_x
crossref_primary_10_1111_j_1749_6632_2001_tb03496_x
crossref_primary_10_1111_j_1538_7836_2011_04337_x
crossref_primary_10_1097_MBC_0b013e32833678d5
crossref_primary_10_1111_j_1538_7836_2006_01722_x
crossref_primary_10_1111_j_1749_6632_2001_tb03536_x
crossref_primary_10_1111_j_1538_7836_2006_02094_x
crossref_primary_10_1016_j_thromres_2013_01_010
Cites_doi 10.1097/00001721-199208000-00002
10.1016/S0021-9258(19)36672-4
10.1016/0005-2736(83)90455-8
10.1126/science.239.4839.487
10.1172/JCI5471
10.1097/00062752-199704050-00010
10.1074/jbc.271.47.30083
10.1159/000205234
10.1016/S0021-9258(17)42399-4
10.1182/blood.V80.8.1972.1972
10.1073/pnas.82.8.2344
10.1046/j.1365-2141.1997.2753090.x
10.1016/S0021-9258(20)30106-X
10.1016/0003-2697(88)90047-4
10.1016/S0268-9499(96)80780-6
10.1074/jbc.271.44.27948
ContentType Journal Article
DBID AAYXX
CITATION
DOI 10.1182/blood.V96.2.773.014k07_773_775
DatabaseName CrossRef
DatabaseTitle CrossRef
DatabaseTitleList CrossRef
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
Chemistry
Biology
Anatomy & Physiology
EISSN 1528-0020
EndPage 775
ExternalDocumentID 10_1182_blood_V96_2_773_014k07_773_775
GroupedDBID ---
-~X
.55
.GJ
0R~
0SF
1CY
23N
2WC
34G
39C
4.4
53G
5GY
5RE
5VS
6J9
9M8
AAEDW
AALRI
AAQQT
AAXUO
AAYXX
ABOCM
ABVKL
ACGFO
ADBBV
ADVLN
AENEX
AFFNX
AFOSN
AI.
AITUG
AKRWK
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
BAWUL
BTFSW
C1A
CITATION
CS3
DIK
DU5
E3Z
EBS
EJD
EX3
F5P
FDB
FRP
GS5
GX1
H13
IH2
J5H
K-O
KQ8
L7B
LSO
MJL
N4W
N9A
OHT
OK1
P2P
R.V
RHF
RHI
ROL
SJN
THE
TR2
TWZ
UCJ
VH1
W2D
W8F
WH7
WOQ
WOW
X7M
YHG
YKV
ZGI
ZXP
ID FETCH-LOGICAL-c1165-27aacdf9f4449dbbad65f6d7be5be8b147a080f21216d43f150b2ab591e30c393
ISSN 0006-4971
IngestDate Fri Aug 23 00:42:08 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 2
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c1165-27aacdf9f4449dbbad65f6d7be5be8b147a080f21216d43f150b2ab591e30c393
PageCount 3
ParticipantIDs crossref_primary_10_1182_blood_V96_2_773_014k07_773_775
PublicationCentury 2000
PublicationDate 2000-07-15
PublicationDateYYYYMMDD 2000-07-15
PublicationDate_xml – month: 07
  year: 2000
  text: 2000-07-15
  day: 15
PublicationDecade 2000
PublicationTitle Blood
PublicationYear 2000
References Neerman-Arbez (2019112004104737400_B16) 1999; 65
Koopman (2019112004104737400_B5) 1992; 80
Nakashima (2019112004104737400_B12) 1992; 3
Zhang (2019112004104737400_B15) 1992; 267
Kant (2019112004104737400_B2) 1985; 82
Xu (2019112004104737400_B17) 1996; 271
Zhang (2019112004104737400_B18) 1996; 271
Martinez (2019112004104737400_B1) 1997; 4
Ciulla (2019112004104737400_B10) 1988; 174
Gorkun (2019112004104737400_B14) 1996; 10
Zhang (2019112004104737400_B19) 1994; 269
Ridgway (2019112004104737400_B4) 1997; 98
Furlan (2019112004104737400_B6) 1994; 269
Neerman-Arbez (2019112004104737400_B7) 1999; 103
Solum (2019112004104737400_B9) 1983; 729
Chung (2019112004104737400_B3) 1995; 3
Saiki (2019112004104737400_B11) 1988; 239
Sherman (2019112004104737400_B13) 1969; 73
Clauss (2019112004104737400_B8) 1957; 17
References_xml – volume: 3
  start-page: 361
  year: 1992
  ident: 2019112004104737400_B12
  article-title: Human fibrinogen heterogeneity: the COOH-terminal residues of defective Aα chains of fibrinogen II.
  publication-title: Blood Coagul Fibrinolysis.
  doi: 10.1097/00001721-199208000-00002
  contributor:
    fullname: Nakashima
– volume: 267
  start-page: 21727
  year: 1992
  ident: 2019112004104737400_B15
  article-title: Identification of Bβ chain domains involved in human fibrinogen assembly.
  publication-title: J Biol Chem.
  doi: 10.1016/S0021-9258(19)36672-4
  contributor:
    fullname: Zhang
– volume: 729
  start-page: 53
  year: 1983
  ident: 2019112004104737400_B9
  article-title: Demonstration of a new glycoprotein Ib-related component in platelet extracts prepared in the presence of leupeptin.
  publication-title: Biochim Biophys Acta.
  doi: 10.1016/0005-2736(83)90455-8
  contributor:
    fullname: Solum
– volume: 3
  start-page: 3223
  year: 1995
  ident: 2019112004104737400_B3
  article-title: Hereditary disorders of fibrinogen and factor XIII.
  publication-title: The metabolic and molecular bases of inherited disease.
  contributor:
    fullname: Chung
– volume: 239
  start-page: 487
  year: 1988
  ident: 2019112004104737400_B11
  article-title: Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
  publication-title: Science.
  doi: 10.1126/science.239.4839.487
  contributor:
    fullname: Saiki
– volume: 103
  start-page: 215
  year: 1999
  ident: 2019112004104737400_B7
  article-title: Deletion of the fibrinogen α-chain gene (FGA) causes congenital afibrinogenemia.
  publication-title: J Clin Invest.
  doi: 10.1172/JCI5471
  contributor:
    fullname: Neerman-Arbez
– volume: 73
  start-page: 574
  year: 1969
  ident: 2019112004104737400_B13
  article-title: In vivo transformation between fibrinogens of varying ethanol solubilities: a pathway of fibrinogen catabolism.
  publication-title: J Lab Clin Med.
  contributor:
    fullname: Sherman
– volume: 4
  start-page: 357
  year: 1997
  ident: 2019112004104737400_B1
  article-title: Congenital dysfibrinogenemia.
  publication-title: Curr Opin Hematol.
  doi: 10.1097/00062752-199704050-00010
  contributor:
    fullname: Martinez
– volume: 271
  start-page: 30083
  year: 1996
  ident: 2019112004104737400_B18
  article-title: Fibrinogen assembly and secretion: role of intrachain disulfide loops.
  publication-title: J Biol Chem.
  doi: 10.1074/jbc.271.47.30083
  contributor:
    fullname: Zhang
– volume: 17
  start-page: 237
  year: 1957
  ident: 2019112004104737400_B8
  article-title: Gerinnungsphysiologische schnellmethode zur bestimmung des fibrinogens.
  publication-title: Acta Haematol.
  doi: 10.1159/000205234
  contributor:
    fullname: Clauss
– volume: 269
  start-page: 652
  year: 1994
  ident: 2019112004104737400_B19
  article-title: Role of interchain disulfide bonds on the assembly and secretion of human fibrinogen.
  publication-title: J Biol Chem.
  doi: 10.1016/S0021-9258(17)42399-4
  contributor:
    fullname: Zhang
– volume: 80
  start-page: 1972
  year: 1992
  ident: 2019112004104737400_B5
  article-title: Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids Aα 461-610 (Lys461 AAA→stop TAA).
  publication-title: Blood.
  doi: 10.1182/blood.V80.8.1972.1972
  contributor:
    fullname: Koopman
– volume: 82
  start-page: 2344
  year: 1985
  ident: 2019112004104737400_B2
  article-title: Evolution and organization of the fibrinogen locus on chromosome 4: gene duplication accompanied by transposition and inversion.
  publication-title: Proc Natl Acad Sci U S A.
  doi: 10.1073/pnas.82.8.2344
  contributor:
    fullname: Kant
– volume: 98
  start-page: 632
  year: 1997
  ident: 2019112004104737400_B4
  article-title: Fibrinogen Otago: a major α chain truncation associated with severe hypofibrinogenaemia and recurrent miscarriage.
  publication-title: Br J Haematol.
  doi: 10.1046/j.1365-2141.1997.2753090.x
  contributor:
    fullname: Ridgway
– volume: 65
  start-page: 2741
  year: 1999
  ident: 2019112004104737400_B16
  article-title: A donor splice site mutation in intron 4 of the fibrinogen α-chain gene (FGA) is the common defect in congenital afibrinogenemia [abstract].
  publication-title: Am J Hum Genet.
  contributor:
    fullname: Neerman-Arbez
– volume: 269
  start-page: 33129
  year: 1994
  ident: 2019112004104737400_B6
  article-title: A frameshift mutation in exon V of the Aα-chain gene leading to truncated Aα-chains in the homozygous dysfibrinogen Milano III.
  publication-title: J Biol Chem.
  doi: 10.1016/S0021-9258(20)30106-X
  contributor:
    fullname: Furlan
– volume: 174
  start-page: 485
  year: 1988
  ident: 2019112004104737400_B10
  article-title: A simple method for DNA purification from peripheral blood.
  publication-title: Anal Biochem.
  doi: 10.1016/0003-2697(88)90047-4
  contributor:
    fullname: Ciulla
– volume: 10
  start-page: 7
  year: 1996
  ident: 2019112004104737400_B14
  article-title: Recombinant fibrinogen in clot formation [abstract].
  publication-title: Fibrinolysis.
  doi: 10.1016/S0268-9499(96)80780-6
  contributor:
    fullname: Gorkun
– volume: 271
  start-page: 27948
  year: 1996
  ident: 2019112004104737400_B17
  article-title: The assembly of human fibrinogen: the role of the amino-terminal and coiled-coil regions of the three chains in the formation of the αγ and βγ heterodimers and αβγ half-molecules.
  publication-title: J Biol Chem.
  doi: 10.1074/jbc.271.44.27948
  contributor:
    fullname: Xu
SSID ssj0014325
Score 1.6522754
Snippet The molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family,...
SourceID crossref
SourceType Aggregation Database
StartPage 773
Title Homozygous truncation of the fibrinogen Aα chain within the coiled coil causes congenital afibrinogenemia
Volume 96
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3NbtQwELaWVhQuCLYg_uUD7WWVkHWcODlmV0UroMChrXqL7MSuSncT1GaF2rdCvAfPxPhnk2xBqPSSWIlmlM18O5mxv_Eg9IYVEAuFSnkkpcSjZaQ8nnDlsUhwgBOHKF8XOO9_imeH9P1xdDwY_OyxlpaN8Iurv9aV3MaqcA3sqqtk_8OyrVK4AGOwLxzBwnC8kY1n9aK-ujzRLNbmfFkVbfino0mlyfxVDcKjbGe6tzMZ6yrfU1u27diNRQ1OoTSnUcGXF_JC09BBRLcSGfFOhVyc8rX137lrMm_DyPm8_m79jSVIjr74XZ4PrtzNslpG2ehze9MURBgr6-qadrangUC6Pj-zHhE-jI6vtJqcCPSspy3PbB1urJvYWfhI52P1ptgBCfpO2La1dWAjPY_KbKcT93Fmts3Kn34_0fvIGq6_f5TGPvFBzof07yxgOQxzJ7i-4fa1D2FLTzSJUUJyoy8HfTkxStb13UGbBLwbuNXNbHL04WO7eEVDYhtnuN--hXbdM7799xP2YqNekHPwED1w2QnOLNQeoYGshmg7q3hTLy7xLjZ8YbMQM0R3J6vRvemqa-AQbe07ssY2-trBE3fwxLXCAD3cYQtnv35gA01soWnuW2iaE7bQxB008TVoPkaH7_YOpjPPtfbwCr3fk0cY50WpUkUpTUsheBlHKi6ZkJGQiRhTxiGVURBXjeOShgrSFkG4iNKxDIMiTMMnaKOqK_kUYUHKWDIVy1QRWoRhwhgEfiDMWUSlTJ8htnqp-Te7g0t-MwM_v7XkC3S_-ze8RBvwkuUrCF4b8dqB5TcGlJoP
link.rule.ids 315,783,787,27936,27937
linkProvider Elsevier
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Homozygous+truncation+of+the+fibrinogen+A%CE%B1+chain+within+the+coiled+coil+causes+congenital+afibrinogenemia&rft.jtitle=Blood&rft.au=Fellowes%2C+Andrew+P.&rft.au=Brennan%2C+Stephen+O.&rft.au=Holme%2C+Randi&rft.au=Stormorken%2C+Helge&rft.date=2000-07-15&rft.issn=0006-4971&rft.eissn=1528-0020&rft.volume=96&rft.issue=2&rft.spage=773&rft.epage=775&rft_id=info:doi/10.1182%2Fblood.V96.2.773.014k07_773_775&rft.externalDBID=n%2Fa&rft.externalDocID=10_1182_blood_V96_2_773_014k07_773_775
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0006-4971&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0006-4971&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0006-4971&client=summon