Homozygous HLA-G*0105N healthy individuals indicate that membrane-anchoredHLA-G1 molecule is not necessary for survival

HLA-G is expected to play an important role during fetal development. Recen tly a healthy individual homozygous for the HLA-G*0105N allele has been des cribed, suggesting that HLA-G expression was not essen tial for fetal survi val. We now report studies of one family with five healthy siblings homozyg ous for HLA-G*0105N, who had been normally delivered; three of these siblin gs were females who also had normal deliveries. In addition, HLA-G*0105N cD NA has been fully sequenced, and normal G1 membrane anchored protein cannot be translated since after the codon 130 cytosine deletion (exon 3) a readi ng frameshift is observed leading to the existence of premature stop codon at position 189 (beginning of exon 4). Other protein isoforms (G2, G3 and G 6), all containing the leader peptide and the ctl domain, are possible and their messenger mRNAs were found; any of these may undertake the necessary HLA-G functions. Our data show that the membrane anchored HLA-G molecule is not necessary in either mother or fetus for a normal pregnancy and surviva l. Also, individuals homozygous for HLA-G*0105N are healthy and with no ind ications of immunodeficiency or autoimmunity.