Molecular genetic prenatal diagnosis of congenital adrenalhyperplasia due to 21-hydroxylase deficiency by allele-specific hybridization

Phyllis W. Speiser, Perrin C. White, Jakob Dupont, Deguang Zhu, Arlene Mercado, Maria I. New

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)367-371
Number of pages5
JournalRecent Progress in Hormone Research
Volume49
Issue number1
StatePublished - 1994

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Prenatal Diagnosis
Molecular Biology
Alleles
Mutation
Chromosomes
Exons
Fetus
Chorionic Villi Sampling
Nonsense Codon
Southern Blotting
Oligonucleotides
Introns
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
Pregnancy
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Molecular genetic prenatal diagnosis of congenital adrenalhyperplasia due to 21-hydroxylase deficiency by allele-specific hybridization. / Speiser, Phyllis W.; White, Perrin C.; Dupont, Jakob; Zhu, Deguang; Mercado, Arlene; New, Maria I.

In: Recent Progress in Hormone Research, Vol. 49, No. 1, 1994, p. 367-371.

Research output: Contribution to journalArticle

Speiser, Phyllis W. ; White, Perrin C. ; Dupont, Jakob ; Zhu, Deguang ; Mercado, Arlene ; New, Maria I. / Molecular genetic prenatal diagnosis of congenital adrenalhyperplasia due to 21-hydroxylase deficiency by allele-specific hybridization. In: Recent Progress in Hormone Research. 1994 ; Vol. 49, No. 1. pp. 367-371.
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