Læknablaðið - 15.06.1995, Blaðsíða 33

LÆKNABLAÐIÐ 1995; 81
477
Væg dreyrasýki A á íslandi
Ólafur Jensson, Sif Jónsdóttir
Jensson Ó, Jónsdóttir S
Mild haemophilia A in Iceland
Læknablaðið 1995; 81: 477-83
A family survey of mild hemophilia A has been
carried out during the last 25 years. Presently these
families contain 27 living affected males or approxi-
mately twice the number of males with severe form
of hemophilia A in Iceland. The aim of the study
was to define the phenotype in three families with
mild haemophilia A and to determine RFLP (Re-
striction Fragment Length Polymorphism) polymor-
phisms, which could support a hypothesis of a com-
mon progenitor of the families. Family survey was
made and index cases were identified in and outside
hospitals and a survey for symptoms and signs of
bleeding in family members and sampling for coag-
ulation and RFLP studies were mostly carried out in
the field. Family members with and without symp-
toms of bleeding were selected for investigation and
normal spouses and unrelated individuals were in-
vestigated for control. Bleeding time, factor VIII
activity, quantification of factor VIII Ag, von Wil-
lebrand factor Ag and vWF ristocetin assay. Typing
of RFLP polymorphisms for genetic homogeneity.
Bleeding manifestations are present in both sexes in
the three families although more frequent and more
severe in the males. Prolonged bleeding time in 6 of
7 affected members in one of the families and sub-
normal levels in von Willebrand related assays point
to an additional abnormality which has not been
explained. The level of factor VIII activity is be-
tween 10-20% in most affected males whereas 35-
60% is found approximately in 2/3 of females carri-
ers and in 1/3 of them factor VIII activity is within
the normal range. Major bleeding episodes in family
Frá erfðafræðideild Blóðbankans. Fyrirspurnir, bréfaskipti:
Ólafur Jensson, Blóðbankanum v/Barónsstíg, 101 Reykja-
vík.
members are associated with accidents, surgical pro-
cedures menorrhagia and in some cases provoked by
diseases such as intestinal ulceration, kidney stones
and abnormalities of vasculature. RFLP polymor-
phisms were detected, which are common to the
families and they support hypothesis of a common
progenitor. The genetic studies show relatively high
prevalence of this type of mild haemophilia A,
which seems to have been present for at least 6-8
generations in Iceland. It is suggested that screening
for this mild haemophilia A gene by molecular ge-
netic method would be of clinical value now, when
it’s mutation has been detected. Transmission of
mild haemophilia A through 6-9 generations is dem-
onstrated by the study. Founder effect is confirmed
by studies of RFLP polymorphisms. The mild hae-
mophilia A type described is the most prevalent of
haemophilia A types in Iceland (population
265,000, 1993).
Ágrip
Gefið er yfirlit um rannsóknir á sex fjöl-
skyldum með væga dreyrasýki A (haemophilia
A) sem hafa verið rannsakaðar á síðustu 25
árum. í þeim greinast nú 27 dreyrasjúkir karlar
og er það um það bil tvöfalt fleiri en núlifandi
karlar með svæsið form af dreyrasýki A. Með
nýlegum sameindaerfðafræðirannsóknum hef-
ur verið sýnt fram á fjórar stökkbreytingar í
geni storkuþáttar VIII (haemophilia A gen)
sem liggja til grundvallar vægri dreyrasýki A í
ofangreindum sex fjölskyldum. I þremur fjöl-
skyldum er urn að ræða sömu stökkbreytingu
sem veldur dreyrasýkinni. Með þessum niður-
stöðum, og reyndar áður einnig með storku-
þáttarrannsóknum, hefur fyrri sjúkdómsgrein-
ing verið leiðrétt, en hún var gerð á þessum
fjölskyldum árið 1970. Skerðibútabreytileikinn
(RFLP = Restriction Fragment Length Poly-
morphism) í þessum fjölskyldum sem fundist
hefur í dreyrasýkigeninu og aðliggjandi svæð-
um þess er sterk vísbending urn skyldleika fjöl-
skyldnanna, sem eiga uppruna í samliggjandi