Abstract
Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by aberrant vascular development such as arteriovenous malformation (AVM). We report here a genetic epidemiologic study in a county, A, in the Akita prefecture (population 1.1 million) located in northern Japan.
Method and subjects: A total of 137 pedigree members were traced of which 81 were alive and 37 were affected by HHT. Complications associated with pulmonary arteriovenous malformations (PAVM) were proven in six out of seven families.
Results: Linkage analysis in two large families complicated with PAVM revealed a linkage to the HHT1 locus (encoding endoglin; ENG). Three novel mutations were found in four families, all of which led to a frame shift: a G to C transversion at the splicing donor site of intron 3 (Inv3+1 G>C) in one family, one base pair insertion (A) at nucleotide 828 (exon 7) of the erdoglin cDNA in two large families (a828-29 ins A), and a four base pair deletion (AAAG) beginning with nucleotide 1120 (exon 8) of the endoglin cDNA (c.1120-1123 delAAAG) in one family. The insertion of A in exon11 (c.147O-1471 insA) mutation was found in one family.
Summary and conclusion: The population prevalence of HHT in the county was estimated to be 1:8,000-1:5,000, roughly comparable with those reported in European and U.S. populations, which is contradictory to the traditional view that HHT is rare among Asians. We recommend that families with HHT be screened for gene mutations in order that high-risk individuals complicated with PAVM receive early diagnosis and treatment initiation that will substantially alter their clinical course and prognosis.
- © 2011 ERS
