caa a22 4500 39757536X CHVBK 20180308164854.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.2039 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.2039 Identification of Non-Amplifying CYP21 Genes When Using PCR-Based Diagnosis of 21-Hydroxylase Deficiency in Congenital Adrenal Hyperplasia (CAH) Affected Pedigrees [Elektronische Daten] [Darren J. Day, Phyllis W. Speiser, Egbert Schulze, M. Bettendorf, Jodene Fitness, Francis Barany, Perrin C. White] 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 androgens, and a severe form of congenital 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. © 1993 Oxford University Press Day Darren J. Victoria University of Wellington, School of Biological Sciences, Box 600, Wellington, New Zealand aut Speiser Phyllis W. Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA aut Schulze Egbert Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany aut Bettendorf M. Department of Paediatrics, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany aut Fitness Jodene Victoria University of Wellington, School of Biological Sciences, Box 600, Wellington, New Zealand aut Barany Francis Department of Microbiology, Hearst Microbiology Research Center, Cornell University Medical College and Strang Cancer Prevention Center, New York, NY 10021, USA aut White Perrin C. University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 2039-2048 0964-6906 5:12<2039 1996 5 hmg https://doi.org/10.1093/hmg/5.12.2039 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.2039 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Day Darren J. Victoria University of Wellington, School of Biological Sciences, Box 600, Wellington, New Zealand aut NATIONALLICENCE 700 1- Speiser Phyllis W. Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA aut NATIONALLICENCE 700 1- Schulze Egbert Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany aut NATIONALLICENCE 700 1- Bettendorf M. Department of Paediatrics, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany aut NATIONALLICENCE 700 1- Fitness Jodene Victoria University of Wellington, School of Biological Sciences, Box 600, Wellington, New Zealand aut NATIONALLICENCE 700 1- Barany Francis Department of Microbiology, Hearst Microbiology Research Center, Cornell University Medical College and Strang Cancer Prevention Center, New York, NY 10021, USA aut NATIONALLICENCE 700 1- White Perrin C. University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9063, USA aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 2039-2048 0964-6906 5:12<2039 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford