HLA-A,B,C,DR typing and 17-OHP determination for second trimester prenatal diagnosis of 21-hydroxylase deficient CAH.
In 18 families at risk for the HLA-linked, 21-hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA-A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17-hydroxyprogesterone (17-OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation. In 16/18 families, both HLA typing of AFC and 17-OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17-OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a 'missed' HLA antigen in one case and to serologically cross-reactive HLA antigens in the second. Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17-OHP measurement was not performed in one family and in the second family the 17-OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus. In conclusion, a combination of HLA typing of cultured AFC and 17-OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA-DR typing of AFC as presented here for the first time proved helpful in families with HLA-A,B homozygosity due to parental sharing of antigens and can be informative for identifying HLA-B/21-OH recombinant haplotypes.
Grosse-Wilde
H
H
Institut für Immungenetik, Universitätsklinikum Essen, F.R.G.
Valentine-Thon
E
E
Vögeler
U
U
Passarge
E
E
Lorenzen
F
F
Sippell
W G
WG
Bidlingmaier
F
F
Knorr
D
D
D019326:17-alpha-Hydroxyprogesterone; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000378:metabolism; D000653:Amniotic Fluid / Q000166:cytology; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006681:HLA-D Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D006908:Hydroxyprogesterones / Q000032:analysis*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000379:methods*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000172:deficiency*
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D006908:Hydroxyprogesterones; D019326:17-alpha-Hydroxyprogesterone; D013250:Steroid Hydroxylases