Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families

Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagi c telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2, Other distinct phenoty pe-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995, All li ving patients and their first-degree relatives were invited to attend a det ailed clinical examination and blood was drawn for mutation analysis. In tw o families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutatio n no individuals with PAVM were identified and only one patient had a histo ry of severe GI bleeding. No mutations in the endoglin locus were found in either family, (C) 2001 Wiley-Liss, Inc.