Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Darren J. Day, Phyllis W. Speiser, Egbert Schulze, M. Bettendorf, Jodene Fitness, Francis Barany, Perrin C. White

Research output: Contribution to journalArticle

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Abstract

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21-hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal and drogens, and a severe form of con genital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.

Original languageEnglish (US)
Pages (from-to)2039-2048
Number of pages10
JournalHuman Molecular Genetics
Volume5
Issue number12
StatePublished - Dec 1996

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Congenital Adrenal Hyperplasia
Pedigree
Steroid 21-Hydroxylase
Polymerase Chain Reaction
Mutation
Genes
Disorders of Sex Development
Inborn Errors Metabolism
Homozygote
Aldosterone
Prenatal Diagnosis
Microsatellite Repeats
Introns
Haplotypes
Hyperplasia
Hydrocortisone
Sodium
Newborn Infant
Messenger RNA
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency

ASJC Scopus subject areas

  • Genetics

Cite this

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees. / Day, Darren J.; Speiser, Phyllis W.; Schulze, Egbert; Bettendorf, M.; Fitness, Jodene; Barany, Francis; White, Perrin C.

In: Human Molecular Genetics, Vol. 5, No. 12, 12.1996, p. 2039-2048.

Research output: Contribution to journalArticle

Day, Darren J. ; Speiser, Phyllis W. ; Schulze, Egbert ; Bettendorf, M. ; Fitness, Jodene ; Barany, Francis ; White, Perrin C. / Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees. In: Human Molecular Genetics. 1996 ; Vol. 5, No. 12. pp. 2039-2048.
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