The molecular basis of haemophilia A and B

被引:27
作者
Giannelli, F
Green, PM
机构
[1] Div. Medical and Molecular Genetics, Med-Dent Sch Guy's-St Thomas Hosps., Guy's Hospital
来源
BAILLIERES CLINICAL HAEMATOLOGY | 1996年 / 9卷 / 02期
基金
英国惠康基金;
关键词
D O I
10.1016/S0950-3536(96)80059-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Most families with haemophilia A or B carry gene defects of independent origin. Haemophilia B is mostly due to small changes in the factor IX gene affecting either its transcription, mRNA maturation, mRNA translation or the fine structure of factor IX. Only 2-3% of patients show gross deletions or rearrangements. The great variety of missense mutations reported to cause haemophilia B indicates that this multidomain protein is highly constrained. Less is known about the factor VIII gene as fully efficient mutation detection procedures only became available in 1991. This, however, led to the discovery that almost half the severe cases of haemophilia A or a fifth of all cases are due to frequently occurring inversions caused by homologous intra-chromosome (-chromatid) recombination between repeated sequences 9.5 kb long. Of the three repeats one is in intron 22 of the factor VIII gene and two are 400-500 kb more telomeric. They are 99.8% similar to each other. The spectrum of the other haemophilia A mutations is similar to that of haemophilia B. Since 1983 mounting evidence has shown that in both haemophilias the nature of the mutation is important in predisposing to the inhibitor complication. With regard to genetic counselling the best way to provide this service is through the construction of national confidential databases of mutations and pedigrees, as indicated by work in the UK on haemophilia B now being extended to haemophilia A.
引用
收藏
页码:211 / 228
页数:18
相关论文
共 64 条
  • [1] ACTIVATION PEPTIDE OF HUMAN FACTOR-IX HAS OLIGOSACCHARIDES O-GLYCOSIDICALLY LINKED TO THREONINE RESIDUES AT 159 AND 169
    AGARWALA, KL
    KAWABATA, S
    TAKAO, T
    MURATA, H
    SHIMONISHI, Y
    NISHIMURA, H
    IWANAGA, S
    [J]. BIOCHEMISTRY, 1994, 33 (17) : 5167 - 5171
  • [2] HEMOPHILIA-A DUE TO MUTATIONS THAT CREATE NEW N-GLYCOSYLATION SITES
    ALY, AM
    HIGUCHI, M
    KASPER, CK
    KAZAZIAN, HH
    ANTONARAKIS, SE
    HOYER, LW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (11) : 4933 - 4937
  • [3] FACTOR-VIII GENE INVERSIONS IN SEVERE HEMOPHILIA-A - RESULTS OF AN INTERNATIONAL CONSORTIUM STUDY
    ANTONARAKIS, SE
    ROSSITER, JP
    YOUNG, M
    HORST, J
    DEMOERLOOSE, P
    SOMMER, SS
    KETTERLING, RP
    KAZAZIAN, HH
    NEGRIER, C
    VINCIGUERRA, C
    GITSCHIER, J
    GOOSSENS, M
    GIRODON, E
    GHANEM, N
    PLASSA, F
    LAVERGNE, JM
    VIDAUD, M
    COSTA, JM
    LAURIAN, Y
    LIN, SW
    LIN, SR
    SHEN, MC
    LILLICRAP, D
    TAYLOR, SAM
    WINDSOR, S
    VALLEIX, SV
    NAFA, K
    SULTAN, Y
    DELPECH, M
    VNENCAKJONES, CL
    PHILLIPS, JA
    LJUNG, RCR
    KOUMBARELIS, E
    GIALERAKI, A
    MANDALAKI, T
    JENKINS, PV
    COLLINS, PW
    PASI, KJ
    GOODEVE, A
    PEAKE, I
    PRESTON, FE
    SCHWARTZ, M
    SCHEIBEL, E
    INGERSLEV, J
    COOPER, DN
    MILLAR, DS
    KAKKAR, VV
    GIANNELLI, F
    NAYLOR, JA
    TIZZANO, EF
    [J]. BLOOD, 1995, 86 (06) : 2206 - 2212
  • [4] CHEN SH, 1988, AM J HUM GENET, V42, P581
  • [5] CHEUNG WF, 1992, J BIOL CHEM, V267, P20529
  • [6] MOLECULAR-CLONING OF THE GENE FOR HUMAN ANTI-HEMOPHILIC FACTOR-IX
    CHOO, KH
    GOULD, KG
    REES, DJG
    BROWNLEE, GG
    [J]. NATURE, 1982, 299 (5879) : 178 - 180
  • [7] RECOVERY FROM HEMOPHILIA-B LEYDEN - AN ANDROGEN-RESPONSIVE ELEMENT IN THE FACTOR-IX PROMOTER
    CROSSLEY, M
    LUDWIG, M
    STOWELL, KM
    DEVOS, P
    OLEK, K
    BROWNLEE, GG
    [J]. SCIENCE, 1992, 257 (5068) : 377 - 379
  • [8] ISOLATION OF AN ACTIVE HUMAN TRANSPOSABLE ELEMENT
    DOMBROSKI, BA
    MATHIAS, SL
    NANTHAKUMAR, E
    SCOTT, AF
    KAZAZIAN, HH
    [J]. SCIENCE, 1991, 254 (5039) : 1805 - 1808
  • [9] FAY PJ, 1991, J BIOL CHEM, V266, P20139
  • [10] CIS-ACTING ELEMENTS AND TRANSCRIPTION FACTORS INVOLVED IN THE PROMOTER ACTIVITY OF THE HUMAN FACTOR-VIII GENE
    FIGUEIREDO, MS
    BROWNLEE, GG
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (20) : 11828 - 11838