title: Homozygous HLA-G*0105N healthy individuals indicate that membrane-anchored HLA-G1 molecule is not necessary for survival.
abstract: HLA-G is expected to play an important role during fetal development. Recently, a healthy individual homozygous for the HLA-G*0105N allele has been described, suggesting that HLA-G expression was not essential for fetal survival. We now report studies of one family with five healthy siblings homozygous for HLA-G*0105N, who had been normally delivered; three of these siblings were females who also had normal deliveries. In addition, HLA-G*0105N cDNA has been fully sequenced, and normal G1 membrane anchored protein cannot be translated since after the codon 130 cytosine deletion (exon 3) a reading frameshift is observed leading to the existence of premature stop codon at position 189 (beginning of exon 4). Other protein isoforms (G2, G3 and G6), all containing the leader peptide and the alpha1 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 survival. Also, individuals homozygous for HLA-G*0105N are healthy and with no indications of immunodeficiency or autoimmunity.
authors.affiliation: Department of Immunology and Molecular Biology, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Casro
authors.forename: P
authors.initials: P
authors.lastname: Morales
authors.forename: R
authors.initials: R
authors.lastname: Rojo-Amigo
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Laso
authors.forename: L
authors.initials: L
authors.lastname: Allende
authors.forename: P
authors.initials: P
authors.lastname: Varela
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Berciano
authors.forename: J
authors.initials: J
authors.lastname: Guillen-Perales
authors.forename: A
authors.initials: A
authors.lastname: Arnaiz-Villena
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D001483:Base Sequence; D018076:DNA, Complementary; D005192:Family Health; D005260:Female; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology* / Q000502:physiology*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D059908:HLA-B13 Antigen; D015236:HLA-C Antigens / Q000276:immunology; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D000097625:HLA-E Antigens
chemical_list: D018076:DNA, Complementary; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D059908:HLA-B13 Antigen; D015236:HLA-C Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D012333:RNA, Messenger; D000097625:HLA-E Antigens; C069526:HLA-A*30 antigen; C420206:HLA-G*01:05N antigen