Mutations found in the Danish population causing Hereditary Hemorrhagic Telangiectasia.

Pernille M Tørring, Klaus Brusgaard, P. Jordan, A. Kjeldsen

Publikation: Konferencebidrag uden forlag/tidsskriftKonferenceabstrakt til konferenceForskningpeer review


University Hospital, Denmark
HHT is an autosomal vascular disorder caused by mutations of either of three loci ENG, ACVLR1 or MADH4. HHT is characterised by recurrent nosebleeds, mucocutaneous telangiectases, and more severe visceral malformations. During the last decade the Danish HHT centre has been performing genetic screening of patients and relatives with HHT. The molecular genetic screening serves dual purposes, a) as part of the clinical management as genotype/phenotype correlations exists, b) to identify asymptomatic family members.

Materials and Methods

Inclusion of patient’s who were talking part in the general clinical HHT management preogram.
Bi-directional sequencing of all exons and exon-intron boundaries of the three loci ENG, ACVLR1 and MADH4 are performed to characterize minor genetic variants. MLPA analysis is performed for all three loci to characterize large rearrangements.

In 61 families we found mutations in either ENG (N=35) or ACVLR1 (N=26). In ENG a total of 22 different mutations were found 16 was unreported. In ACVLR1 24 different mutations were found 13 was unreported. The mutations were mainly of a familial character all though in ENG a single mutation is present in 11 families and 2 mutations are represented in 2 families. Likewise in ACVLR1 2 mutations was found in 2 different families. I ENG 1 and in ACVLR1 3 families had major deletions found by MLPA. No mutations were found in MADH4.

The majority of mutations found during clinical genetic screening in HHT will be of a family specific kind. Proper analysis requires performing investigation for major deletions as well.
Publikationsdato4. mar. 2011
StatusUdgivet - 4. mar. 2011

Bibliografisk note

The 9th Hereditary Hemorrhagic Telangiectasia (HHT) Scientific Conference, Kemer, Turkey