Antenatal Membranous Nephropathy and Type 2 (Axonal) Charcot-Marie-Tooth With Mutations in the Metallo-Membrane Endopeptidase Gene: A Call for Family Screening and Pharmacovigilance

摘要

In 2002, two of us (HD, PR) identified the first human podocyte antigen, neutral endopeptidase (NEP), in membranous nephropathy (MN) in a French child of Portuguese origin who was born with the nephrotic syndrome. 1 MN could be experimentally reproduced in rabbit infused with the mother’s serum that contained anti-NEP antibodies. The mother was deficient in NEP and thus became immunized at a previous miscarriage against the NEP antigen presented by placenta cells. The consequence of this allo-immunization process was the transplacental passage of anti-NEP antibodies dur- ing the last trimester of pregnancy that caused the development of MN in the offspring. Two other fam- ilies from the Netherlands and Morocco (living in Belgium) were then investigated, which led to identi- fication of the cause of NEP deficiency as a truncating mutation in MME, the gene coding for NEP. 2 Two additional families from Italy and Germany were sub- sequently reported with the same homozygous trun- cating mutation c.466delC (p.Pro156Leufs*14).