TY - JOUR
T1 - Molecular genetic prenatal diagnosis of congenital adrenalhyperplasia due to 21-hydroxylase deficiency by allele-specific hybridization
AU - Speiser, Phyllis W.
AU - White, Perrin C.
AU - Dupont, Jakob
AU - Zhu, Deguang
AU - Mercado, Arlene
AU - New, Maria I.
PY - 1994
Y1 - 1994
N2 - The feasibility and accuracy of gene-specific molecular genetic diagnosis for congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency were studied in a group of 24 pregnancies at 25% risk of carrying an affected fetus. Chorionic villus sampling was performed in the majority of cases. Southern blot analysis was carried out to identify deletions or other gross rearrangements. In parallel, the polymerase chain reaction (PCR) was performed, followed by allele-specific oligonucleotide hybridization (ASO) for a panel of nine known mutations. Mutations were identified in 95% of the chromosomes examined. The molecular diagnosis was accurate in 23 of 24 infants. The most common mutation identified was an A-to-G transition in the second intron (52% of affected chromosomes), the result of an apparent conversion, one fetus carried homozygous deletion of CYP21, which accounted for 13% of all affected chromosomes. Other mutations identified included an 8-bp deletion in the third exon (22%); Ile172 to Asn, a nonconservative substitution, in the fourth exon (9%); and Gln318 to term, a nonsense mutation, in the eighth exon (4%). No mutation was detected in CYP21 in 5% of obligate-affected chromosomes examined by these methods.
AB - The feasibility and accuracy of gene-specific molecular genetic diagnosis for congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency were studied in a group of 24 pregnancies at 25% risk of carrying an affected fetus. Chorionic villus sampling was performed in the majority of cases. Southern blot analysis was carried out to identify deletions or other gross rearrangements. In parallel, the polymerase chain reaction (PCR) was performed, followed by allele-specific oligonucleotide hybridization (ASO) for a panel of nine known mutations. Mutations were identified in 95% of the chromosomes examined. The molecular diagnosis was accurate in 23 of 24 infants. The most common mutation identified was an A-to-G transition in the second intron (52% of affected chromosomes), the result of an apparent conversion, one fetus carried homozygous deletion of CYP21, which accounted for 13% of all affected chromosomes. Other mutations identified included an 8-bp deletion in the third exon (22%); Ile172 to Asn, a nonconservative substitution, in the fourth exon (9%); and Gln318 to term, a nonsense mutation, in the eighth exon (4%). No mutation was detected in CYP21 in 5% of obligate-affected chromosomes examined by these methods.
UR - http://www.scopus.com/inward/record.url?scp=0028141325&partnerID=8YFLogxK
U2 - 10.1016/b978-0-12-571149-4.50026-x
DO - 10.1016/b978-0-12-571149-4.50026-x
M3 - Article
C2 - 8146433
AN - SCOPUS:0028141325
SN - 0079-9963
VL - 49
SP - 367
EP - 371
JO - Recent Progress in Hormone Research
JF - Recent Progress in Hormone Research
IS - 1
ER -