Læknablaðið - 15.01.1999, Page 37

LÆKNABLAÐIÐ 1999; 85
33
Blöðrunýrnasjúkdómur meö
ríkjandi erfðamáta á íslandi
Erfðafræðileg rannsókn
Ragnheiður Fossdal1, Magnús Böðvarsson2, Páll Ásmundsson2, Jóhann Ragnarsson3, Runólfur
Pálsson2
Fossdal R, Böðvarsson M, Ásmundsson P, Ragn-
arsson J, Pálsson R
Autosomal dominant polycystic kidney discasc in
Iceland - genetic study
Læknablaðið 1999; 85; 33-42
Objective: Autosomal dominant polycystic kidney
disease (ADPKD) is one of the most common gene-
tic diseases in humans and accounts for 8-10% of
end-stage renal failure. The disease is caused by mu-
tations in at least three different genes. About 85% of
families with ADPKD have a mutation in a gene
(PKDl) on chromosome 16p, whereas 10-15% have
a mutation in a gene (PKD2) on chromosome 4q. In
a few families, a third gene (PKD3) of unknown lo-
cation appears to be involved. The purpose of this
study was to determine the genotype of Icelandic
families with ADPKD.
Material and methods: We isolated DNA from 229
family members and generated genotypes for poly-
morphic markers with conventional methods. Link-
age analysis and haplotype analysis were performed
in 14 ADPKD families, employing markers from the
PKDl and PKD2 regions.
Results: The abnormal gene could be located in 13
families. Eleven families demonstrated linkage to the
PKDl locus and two families to the PKD2 locus.
Comparison of the haplotypes of the PKDl families
indicates that nine different mutations cause ADPKD1
in Iceland, including one de novo mutation. The two
ADPKD2 families each have a distinct haplotype.
Frá "íslenskri erfðagreiningu, 2lblóðskilunardeild og lyf-
lækningadeild Landspítalans, 3llyflækningadeild Sjúkrahúss
Reykjavíkur. Fyrirspurnir, bréfaskipti: Ragnheiður Fossdal,
Islenskri erfðagreiningu, Lynghálsi 1, 110 Reykjavík. Sími:
570 1977. Bréfsími: 570 1903. Netfang: fossdal@decode.
is
Lykilorð: arfgeng blöörunýru, meingen, lengslagreining,
setraöagreining, litningur 16, Iitningur4, stökkbreyting.
Therefore, at least 11 different mutations cause
ADPKD in Iceland. In cooperation with Dutch scien-
tists, one mutation in the PKD2 gene was defined, a
16 bp deletion of a splice site between intron 1 and
exon 2.
Conclusions: Our results demonstrate marked gene-
tic heterogeneity of ADPKD in the Icelandic popula-
tion. As expected, most of the families have evidence
for mutation in the PKDl gene. The stage has been
set for future work, which will focus on detecting
mutations in the PKD genes and defining the cor-
relation between mutations and the phenotype of the
disease.
Key words: potycystic kidney disease, gene, linkage ana-
lysis, haplotype analysis. chromosome 16, chromosome 4,
mutation
Ágrip
Tilgangur: Blöðrunýmasjúkdómur með ríkj-
andi erfðamáta (arfgeng blöðmným, autosomal
dominant polycystic kidney disease, ADPKD) er
einn algengasti erfðasjúkdómur sem þekkist hjá
mönnum og veldur urn 8-10% af lokastigsnýrna-
bilun. Stökkbreytingar í að minnsta kosti þremur
genum orsaka sjúkdóminn. Um 85% þeirra eru í
geni (PKDl) á litningi 16p og 10-15% í geni
(PKD2) á litningi 4q. Auk þess hefur fáeinunr
fjölskyldum verið lýst þar sem ekki hefur tekist
að staðsetja meingenið. Tilgangur þessarar rann-
sóknar var að skilgreina arfgerð íslenskra fjöl-
skyldna með arfgengan blöðmnýmasjúkdóm.
Efniviður og aðferðir: Erfðaefni var ein-
angrað úr blóðsýnum 229 einstaklinga í 14
blöðrunýrnafjölskyldum. Tengsla- og setraða-
greining var síðan gerð með þekktum erfða-
mörkum fyrir bæði meingenasvæðin (PKDl og
PKD2).
Niðurstöður: Unnt var að segja til um stað-
setningu meingensins í 13 fjölskyldum. Ellefu