Premium
Mutations in endoglin and in activin receptor‐like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia
Author(s) -
Brusgaard K,
Kjeldsen AD,
Poulsen L,
Moss H,
Vase P,
Rasmussen K,
Kruse TA,
Hørder M
Publication year - 2004
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2004.00341.x
Subject(s) - acvrl1 , mutation , genetics , chromosome , biology , danish , population , genotype , endoglin , genetic heterogeneity , medicine , phenotype , gene , linguistics , philosophy , stem cell , environmental health , cd34
Hereditary haemorrhagic telangiectasia (HHT) is a rare disorder with one per 6000–10,000 affected individuals in the general Caucasian population. HHT is genetically heterogeneous, involving at least two loci HHT1 mapping to chromosome 9q34.1 and HHT2 mapping to chromosome 12q31. The loci have been identified as endoglin (ENG) and activin receptor‐like kinase 1 (ALK1). In order to gain knowledge of the genotype distribution and prevalence in the Danish population and to establish a reproducible and sensitive molecular genetic test method, we developed a denaturating gradient gel electrophoresis protocol for mutation scanning of the two loci. Twenty‐five Danish HHT families were tested. A total of eight new as well as seven previously reported mutations were identified. A founder mutation was characterized present in seven families and possibly introduced around 350 years ago. In one individual, a presumed spontaneous mutation was characterized. The method developed proved to be very sensitive for mutation detection in both ENG and ALK1. Genetic screening in HHT families facilitates an early treatment strategy for silent HHT manifestations in first degree relatives.