Endoglin expression is reduced in normal vessels but still detectable in arteriovenous malformations of patients with hereditary hemorrhagic telangiectasia type 1

Endoglin is predominantly expressed on endothelium and is mutated in heredi tary hemorrhagic telangiectasia (HHT) type 1 (HHT1). We report the analysis of endoglin in tissues of a newborn (family 2), who died of a cerebral art eriovenous malformation (CAVM), and in a lung specimen surgically resected from a 78-year-old patient (family 5), with a pulmonary AVM (PAVM). The cli nically affected father of the newborn revealed a novel mutation that was a bsent in his parents and was identified as a duplication of exons 3 to 8, b y quantitative multiplex polymerase chain reaction. The corresponding mutan t protein (116-kd monomer) and the missense mutant protein (80-kd monomer) present in family 5 were detected only as transient intracellular species a nd were unreactive by Western blot analysis and immunostaining. Normal endo glin (90-kd monomer) was reduced by 50% on peripheral blood-activated monoc ytes of the HHT1 patients. When analyzed by immunostaining and densitometry , presumed normal blood vessels of the newborn lung and brain and vessels a djacent to the adult PAVM showed a 50% reduction in the endoglin/PECAM-1 ra tio. A similar ratio was observed in the CAVM and PAVM, suggesting that all blood vessels of HHT1 patients express reduced endoglin in situ and that A VMs are not attributed to a focal loss of endoglin.