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Molecular Diagnostics and Genetics |
a Author for correspondence. Fax 49-89-5160-4784; e-mail hp.schwarz{at}kk-i.med.uni-muenchen.de.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease
with a wide range of clinical manifestations. It is most often caused
by deficiency of steroid 21-hydroxylase, reflecting any of a wide range
of mutations in the 21-hydroxylase (CYP21) gene. A
major challenge in molecular diagnostics of CAH is the high homology
between the CYP21 gene and the CYP21P
pseudogene and the phenomenon of apparent gene conversion, which
inactivates the functional gene. In this study we devised an improved
stepwise diagnostic procedure involving nonradioactive Southern
blotting and direct DNA sequencing. This strategy led to a successful
elucidation of the molecular cause of the disease in 181 out of 182
unrelated alleles in a total of 91 clinically and biochemically
characterized patients. We were able to identify all classical known
disease-causing mutations of the 21-hydroxylase gene and a novel
nonsense mutation (bp 670, A
C, Y97X). Our method also allows the
reliable, secure diagnosis of the heterozygous configuration and may
therefore be used for pre-, peri-, and postnatal diagnosis of CAH, even
when informative data of the index patient are lacking. Furthermore, it
can be used to confirm the diagnosis of CAH in newborns detected in
17-hydroxyprogesterone screening programs.
The following articles in journals at HighWire Press have cited this article:
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  F. G. Riepe, S. Tatzel, W. G. Sippell, J. Pleiss, and N. Krone Congenital Adrenal Hyperplasia: The Molecular Basis of 21-Hydroxylase Deficiency in H-2aw18 Mice Endocrinology, June 1, 2005; 146(6): 2563 - 2574. [Abstract] [Full Text] [PDF]
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 D. Keen-Kim, J. B. Redman, R. U. Alanes, M. M. Eachus, R. C. Wilson, M. I. New, J. M. Nakamoto, and R. G. Fenwick Validation and Clinical Application of a Locus-Specific Polymerase Chain Reaction- and Minisequencing-Based Assay for Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) J. Mol. Diagn., May 1, 2005; 7(2): 236 - 246. [Abstract] [Full Text] [PDF]
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 N. Krone, F. G. Riepe, J. Grotzinger, C.-J. Partsch, and W. G. Sippell Functional Characterization of Two Novel Point Mutations in the CYP21 Gene Causing Simple Virilizing Forms of Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 445 - 454. [Abstract] [Full Text] [PDF]
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 R. Rej Clinical Chemistry through Clinical Chemistry: A Journal Timeline Clin. Chem., December 1, 2004; 50(12): 2415 - 2458. [Abstract] [Full Text] [PDF]
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H.-H. Lee, Y.-J. Lee, P. Chan, and C.-Y. Lin Use of PCR-Based Amplification Analysis as a Substitute for the Southern Blot Method for CYP21 Deletion Detection in Congenital Adrenal Hyperplasia Clin. Chem., June 1, 2004; 50(6): 1074 - 1076. [Full Text] [PDF]
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H.-H. Lee, S.-F. Chang, F.-J. Tsai, L.-P. Tsai, and C.-Y. Lin Mutation of IVS2 -12A/C>G in Combination with 707-714delGAGACTAC in the CYP21 Gene Is Caused by Deletion of the C4-CYP21 Repeat Module with Steroid 21-Hydroxylase Deficiency J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2726 - 2729. [Abstract] [Full Text] [PDF]
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M. P. Caulfield, T. Lynn, M. E. Gottschalk, K. L. Jones, N. F. Taylor, E. M. Malunowicz, C. H. L. Shackleton, R. E. Reitz, and D. A. Fisher The Diagnosis of Congenital Adrenal Hyperplasia in the Newborn by Gas Chromatography/Mass Spectrometry Analysis of Random Urine Specimens J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3682 - 3690. [Abstract] [Full Text] [PDF]
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N. Krone, A. Braun, S. Weinert, M. Peter, A. A. Roscher, C.-J. Partsch, and W. G. Sippell Multiplex Minisequencing of the 21-Hydroxylase Gene as a Rapid Strategy to Confirm Congenital Adrenal Hyperplasia Clin. Chem., June 1, 2002; 48(6): 818 - 825. [Abstract] [Full Text] [PDF]
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S. M. Baumgartner-Parzer, E. Schulze, W. Waldhausl, S. Pauschenwein, S. Rondot, P. Nowotny, K. Meyer, H. Frisch, F. Waldhauser, and H. Vierhapper Mutational Spectrum of the Steroid 21-Hydroxylase Gene in Austria: Identification of a Novel Missense Mutation J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4771 - 4775. [Abstract] [Full Text] [PDF]
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 P. C. White and P. W. Speiser Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Endocr. Rev., June 1, 2000; 21(3): 245 - 291. [Abstract] [Full Text]
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N. Krone, A. Braun, A. A. Roscher, D. Knorr, and H. P. Schwarz Predicting Phenotype in Steroid 21-Hydroxylase Deficiency? Comprehensive Genotyping in 155 Unrelated, Well Defined Patients from Southern Germany J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1059 - 1065. [Abstract] [Full Text]
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A. W. Root Editorial: Neonatal Screening for 21-Hydroxylase Deficient Congenital Adrenal Hyperplasia--The Role of CYP21 Analysis J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1503 - 1504. [Full Text]
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