GJA4 and lymphedema: An implication of our finding that Cx37 haplodeficiency results in dysfunctional valves is that human patients with loss-of-function mutations in one allele of GJA4 are predicted to experience some degree of primary lymphedema and, indeed, whole exome sequencing of patients with primary lymphedema has recently revealed potential pathological variants of GJA4 (personal communications from Miikka Vikkula, de Duve Institute, Brussels, Belgium; and Pia Ostergaard, St.