title: The frequency and the effects of 21-hydroxylase gene defects in congenital adrenal hyperplasia patients.
abstract: Congenital adrenal hyperplasia (CAH) is a group of genetic endocrine disorders, caused by enzyme deficiencies in the conversion of cholesterol to cortisol. More than 90% of the cases have 21-hydroxylase deficiency (21-OHD). The clinical phenotype of the disease is classified as classic, the severe form, and nonclassic, the mild form. In this study, it was planned to characterize the mutations that cause 21-OHD in Turkish CAH patients by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis and to investigate the type of CAH (classic or nonclassic type) that these mutations cause. A total of 124 CAH patients with 21-OHD and 100 healthy volunteers were recruited to the study. Most of the mutations were detected by direct sequencing. Large gene deletions/duplications/conversions were investigated with MLPA analysis. Results were evaluated statistically. At the end of our study, 66 different variations were detected including SNPs and deletions/duplications/conversions. Of these variations, 18 are novel, of which three cause amino acid substitutions. In addition, 15 SNPs which cause amino acid changes were identified among these variations. If similar results are obtained in different populations, these mutations, in particular the novel mutation 711 G>A, may be used as markers for prenatal diagnosis.
authors.affiliation: Yeditepe University, Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirac
authors.affiliation: Marmara University, Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey.
authors.forename: Ahmet Ilter
authors.initials: AI
authors.lastname: Guney
authors.affiliation: Bakırkoy Dr. Sadi Konuk Hospital, Department of Pediatric Endocrinology, Istanbul, Turkey.
authors.forename: Teoman
authors.initials: T
authors.lastname: Akcay
authors.affiliation: Marmara University, Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey.
authors.forename: Tulay
authors.initials: T
authors.lastname: Guran
authors.affiliation: Marmara University, Faculty of Dentistry, Department of Medical Biology and Genetics, Istanbul, Turkey.
authors.forename: Korkut
authors.initials: K
authors.lastname: Ulucan
authors.affiliation: Marmara University, Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Turan
authors.affiliation: Marmara University, Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ergec
authors.affiliation: Marmara University, Faculty of Medicine, Department of Medical Genetics, Istanbul, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Koc
authors.affiliation: Marmara University, Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.affiliation: Yeditepe University, Faculty of Medicine, Department of Biostatistics, Istanbul, Turkey.
authors.forename: Elif Cigdem
authors.initials: EC
authors.lastname: Kaspar
authors.affiliation: Marmara University, Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Bereket
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005785:Gene Conversion; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D014421:Turkey
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase
keywords: 21‐OHD; CAH; CYP21A2; MLPA analysis; direct sequencing