Findings in Patients 1 and 2, together with data on mCcbe1 expression [34] and CCBE1mutations in forms of lymphedema unaccompanied by cholestasis [7-10], suggest that CCBE1 may be most critical for lymphatic development, but plays a supporting role in hepatic development, such that in some patients with CCBE1 deficiency, hepatobiliary disease (cholestasis) occurs. Here, CCBE1 is linked to lymphedema.