Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Horm Res Paediatr 2010;74:182–189 DOI: 10.1159/000281417 Three Novel CYP11B1 Mutations in Congenital Adrenal Hyperplasia due to Steroid 11Beta- Hydroxylase Deficiency in a Moroccan Population L. Chabraoui   a F. Abid   a R. Menassa   b A. Gaouzi   c A. El Hessni   d Y. Morel   b a  Laboratoire de biochimie, Centre d’étude des maladies héréditaires du métabolisme, CHU Ibn-Sina, Université Mohammed-V-Souissi, Rabat, Maroc; b  Laboratoire d’endocrinologie moléculaire et maladies rares, Université de Lyon et Centre de biologie et pathologie est, Bron, France; c  Service de Pédiatrie 2, Hôpital d’enfants de Rabat, Rabat, d  Laboratoire de physiologie nerveuse et endocrinienne, Faculté des sciences, Université Ibn-Toufail , Kenitra, Maroc mutation, we could deduce from their phenotype and our modeling studies that the p.Gly446Val mutation was more severe than p.Ala259Asp. Conclusion: This study shows a good correlation between phenotype and genotype. Each CYP11B1 mutation is new and private, contrasting with the high incidence of two Tunisian mutations. Copyright © 2010 S. Karger AG, Basel Introduction Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by an inherited de- fect in cortisol biosynthesis [1, 2]. Steroid 11 -hydroxy- lase deficiency (11OHD) is the second most common cause of CAH but accounts only for 5% of all CAH ac- cording to two old national reports before molecular studies [3, 4]. In our large cohort of about 1,700 CAH cases in which the genetic lesions have been identified, 11OHD accounts for 8% of CAH, but its higher incidence could be biased by our recruitment. Recently, the screen- Key Words 11 -Hydroxylase  Congenital adrenal hyperplasia  CYP11B1 gene Abstract Background/Aims: Steroid 11 -hydroxylase deficiency (11OHD), the second cause of congenital adrenal hyperplasia (CAH), accounts only for 5% of all CAH. To date, only 51 dif- ferent mutations have been reported with poor clinical and biological data. Most of them could be considered as private mutations except one, p.R448H, identified especially in Mo- roccan Jews but also in Caucasian patients. As two other CYP11B1 mutations have a high incidence in Tunisian pa- tients, we report from another Maghreb population the clin- ical, follow-up and molecular genetics of 5 Moroccan pa- tients with classical 11OHD. Methods: Patients belonging to 3 families were recruited on clinical data. The diagnosis was confirmed by 11-deoxycortisol determination. Sequencing of the CYP11B1 gene and molecular modeling were per- formed. Results: Clinical, hormonal and follow-up data were consistent with a severe form of 11OHD. Gender reassign- ment and evolution of hypertension were discussed. Three novel mutations, p.Ala259Asp, p.Gly446Val and IVS5+2T 1G were identified. As each patient was homozygous for one Received: June 24, 2009 Accepted: December 30, 2009 Published online: June 3, 2010 Prof. Yves Morel Laboratoire d’endocrinologie moléculaire et maladies rares Centre de biologie et de pathologie est, Centre hospitalier est 59, boulevard Pinel, FR–69677 Bron cedex (France) Tel. +33 4 72 12 96 83, Fax +33 4 72 12 97 20, E-Mail yves.morel  @  chu-lyon.fr © 2010 S. Karger AG, Basel 1663–2818/10/0743–0182$26.00/0 Accessible online at: www.karger.com/hrp HORMONE RESEARCH IN PÆDIATRICS L.C. and F.A. contributed equally to this work and should be consid- ered as equal first authors.