caa a22 4500 467985685 CHVBK 20180323112531.0 cr unu---uuuuu 170328e19901001xx s 000 0 eng 10.1007/BF00194218 doi (NATIONALLICENCE)springer-10.1007/BF00194218 Taq I HLA-B and -DRB RFLP analysis can predict disease in siblings of affected children with 21-hydroxylase deficiency [Elektronische Daten] [Olle Olerup, Holger Luthman, E. Martin Ritzén, Barbro Haglund-Stengler] Summary: The possibility of using TaqI restriction fragment length polymorphism (RFLP) analysis of the HLA-B locus and the HLA-DR-DQ subregions, flanking the 21-hydroxylase genes, for predicting disease in siblings of children with 21-hydroxylase deficiency was analyzed in 12 nuclear families with at least one affected child and a total of 18 at-risk off-spring. As part of the study allelic TaqI HLA-B RFLP patterns were determined in homozygous cell lines and families. The frequencies of individuals homozygous for TaqI allelic patterns of the different investigated HLA loci, each locus alone and in various combinations, were determined in 100 random controls. In all 12 families it was possible to make correct genetic diagnosis by the use of only one restriction enzyme, TaqI, and two locus-specific HLA cDNA probes, HLA-B and -DRB. In all families four haplotypes were obtained. Thus, affected siblings as well as carriers could be identified. Seven of the eight sibling pairs concordant for 21-hydroxylase deficiency had pairwise identical TaqI HLA-B-DRB-DQA-DQB haplotypes. The last disease-concordant sibling pair had inherited different haplotypes from their mother, who had nonclassical 21-hydroxylase deficiency. None of the ten healthy children shared both haplotypes with their affected sibling(s). Early prenatal suppression of the fetal adrenal cortex with fluorinated corticosteroids can prevent virilization of female fetuses with 21-hydroxylase deficiency. In most cases RFLP analysis of the 21-hydroxylase genes is not informative enough for prenatal diagnosis. Our results from the present retrospective family study indicate that TaqI HLA-B and -DRB RFP analysis will be a valuable tool for first trimester assessment of 21-hydroxylase deficiency. TagI HLA-B and -DRB RFLP analysis can be performed on DNA from chorionic villi biopsies obtained in the 8th week of pregnancy. Supplemented with sex determination, early withdrawal of prophylactic steroid therapy will thus be feasible when the mother carries a male or an unaffected female fetus. Springer-Verlag, 1990 Olerup Olle Center for BioTechnology, Karolinska Institute, NOVUM, S-14152, Huddinge, Sweden aut Luthman Holger Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut Martin Ritzén E. Department of Pediatric Endocrinology, Karolinska Hospital, S-10401, Stockholm, Sweden aut Haglund-Stengler Barbro Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut Human Genetics Springer-Verlag 85/5(1990-10-01), 467-472 0340-6717 85:5<467 1990 85 439 https://doi.org/10.1007/BF00194218 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00194218 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Olerup Olle Center for BioTechnology, Karolinska Institute, NOVUM, S-14152, Huddinge, Sweden aut NATIONALLICENCE 700 1- Luthman Holger Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 700 1- Martin Ritzén E. Department of Pediatric Endocrinology, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 700 1- Haglund-Stengler Barbro Department of Clinical Genetics, Karolinska Hospital, S-10401, Stockholm, Sweden aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 85/5(1990-10-01), 467-472 0340-6717 85:5<467 1990 85 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer