MUTATION AND ENDOGLIN UP-REGULATION ANALYSES IN A HHT1 FAMILY
This study assumed a HHT1 phenotype for a1167, although the endoglin mutation was confirmed in fewer than one half (27 patients) of them.
Thus, not only in HHT1, but also in HHT2 patients, the percentage of endoglin increase in activated monocytes is age-dependent and is related to the severity of clinical symptoms (Fig.
Haploinsufficiency is the molecular basis currently accepted for the clinical manifestations in HHT1 and HHT2 patients (3, 20, 22).
The relative deficiency of endoglin in activated monocytes from HHT1 patients is expected and has been used as complementary to endoglin analysis in HUVECs (newborns) and in mutation studies to differentiate between HHT1 and HHT2 families (10).
HHT1 patients have, in theory, one half the endoglin concentrations of healthy individuals, and this haploinsufficiency may impair the feedback regulation, leading, in the long term, to impaired endoglin production as is observed in older patients.
that endoglin haploinsufficiency is the ultimate trigger mechanism underlying not only HHT1, but also HHT2.