Hereditary haemorrhagic telangiectasia (HHT) affects one in 5−8000, and no longer can be viewed as solely causing anaemia (due to nasal and gastrointestinal bleeding) and characteristic mucocutaneous telangiectasia. Arteriovenous malformations commonly occur, and in the pulmonary and cerebral circulations demand knowledge of risks and benefits of asymptomatic screening and treatment. HHT is inherited as an autosomal dominant trait and there is no age cut off when apparently unaffected offspring of an individual with HHT can be told they are unaffected. This review focuses on the evolving evidence base for HHT management, issues regarding pregnancy and prothrombotic treatments, and discusses the molecular and cellular changes that underlie this disease.
Methods-Family members were assessed clinically to assign HHT disease status and were screened for PAVMs. DNA was extracted from blood obtained from 20 individuals of known disease status. Short tandem repeat polymorphic markers spanning the intervals containing the endoglin and ALK-1 genes were amplified by the polymerase chain reaction using 33 P-labelled oligonucleotide primers, separated by denaturing polyacrylamide gel electrophoresis (PAGE), and the resultant autoradiographs were examined for allele sizes. Linkage analyses were performed using MLINK and GENE-HUNTER. Results-Twelve members spanning four generations were aVected with HHT. Two had proven PAVMs, one with a classical appearance, the other exhibiting microscopic PAVMs exacerbated by pregnancy. Two point lod and multipoint lod scores significantly excluded linkage to endoglin and ALK-1 in this pedigree. Conclusions-This study confirms the existence of a third HHT locus that accounts for disease in some HHT patients with pulmonary involvement. (Thorax 2000;55:685-690)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.