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

Human Molecular Genetics
D J DayP C White

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 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.

Citations

Jun 8, 2001·The Journal of Molecular Diagnostics : JMD·C E Keegan, A A Killeen
Apr 25, 2007·Nature Clinical Practice. Endocrinology & Metabolism·Saroj Nimkarn, Maria I New
Jan 7, 1999·Clinical Endocrinology·P W Speiser, P C White
Aug 22, 2003·The New England Journal of Medicine·Phyllis W Speiser, Perrin C White
Oct 11, 2012·Genetic Testing and Molecular Biomarkers·Pernille M TørringKlaus Brusgaard
May 5, 2000·Archives of Disease in Childhood. Fetal and Neonatal Edition·C G Brook
Jan 23, 2013·The Journal of Clinical Endocrinology and Metabolism·Nils KroneUNKNOWN United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)
Aug 15, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·P W Speiser
Nov 22, 2001·Journal of Endocrinological Investigation·P W Speiser
Nov 8, 2013·Nucleic Acids Research·Carsten A RaabeTimofey S Rozhdestvensky
Nov 26, 2011·Best Practice & Research. Clinical Endocrinology & Metabolism·Oksana Lekarev, Maria I New
Jul 30, 2004·The Australian & New Zealand Journal of Obstetrics & Gynaecology·Darren J DayStella Milsom
Apr 16, 2010·Annals of the New York Academy of Sciences·Saroj Nimkarn, Maria I New
Jun 18, 2002·Best Practice & Research. Clinical Endocrinology & Metabolism·Perrin C White, Phyllis W Speiser
Dec 23, 2008·Molecular and Cellular Endocrinology·Saroj Nimkarn, Maria I New
May 2, 2015·Biosensors & Bioelectronics·Yanting ShenZuhong Lu
Jan 21, 2014·Experimental Cell Research·Erwin L van DijkClaude Thermes
Jul 27, 2001·Best Practice & Research. Clinical Endocrinology & Metabolism·P C White
Dec 24, 2010·Journal of Pediatric Endocrinology & Metabolism : JPEM·Violeta Anastasovska, Mirjana Kocova
Jan 18, 2005·Revista do Hospital das Clínicas·Priscilla CukierAna Elisa C Billerbeck
Sep 24, 1999·Journal of Molecular Biology·N P GerryF Barany
Sep 16, 1999·Critical Reviews in Clinical Laboratory Sciences·C A Stratakis, O M Rennert
Aug 20, 2009·Nature Reviews. Endocrinology·Perrin C White
Dec 16, 2003·European Journal of Human Genetics : EJHG·Andrew J WalleyAdrian V S Hill
Dec 12, 2018·Endocrine Connections·Sandra Rinne DahlPer Medbøe Thorsby
Sep 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Ana Elisa C BillerbeckTânia A S S Bachega
Apr 13, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Daniel J TurnerFrancis Barany
Oct 19, 2006·Hormone Research·Saroj Nimkarn, Maria I New
May 1, 2007·Expert Reviews in Molecular Medicine·João GonçalvesLuís Moura
Jan 20, 2004·Journal of Human Genetics·Hsien-Hsiung Lee

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