Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency
| Autor: | Jessica Estatico, Miroslav Dumić, Mona Hafez, Assaf Holtzman, Paul Martin Holterhus, Ali Saad, Marco Cappa, Di Li, Maria I. New, Raquel Romero, James T. Burns, Alicia Belgorosky, Nazli Gonc, Mone Zaidi, Tina Cheng, Noha Musa, Nurgun Kandemir, Berenice B. Mendonca, Saleel Fatima, Dauood Alam, Ahmed Khattab, Javier Aisenberg, Sun Li, Munier Nour, Simran Rahi, Samarth Dhawan, Ali S. Alzahrani, Najoua Khaloul, Danièle Pacaud, Ursula Kuhnle-Krahl, Ilhem Charfeddine, Tony Yuen, Alev Ozon, Ameet Kumar, Katja Dumic, Moez Gribaa, Shozeb Haider, Maryam Razzghy Azar, Ayfer Alikasifoglu |
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| Přispěvatelé: | Çocuk Sağlığı ve Hastalıkları |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
MISSENSE MUTATIONS
0301 basic medicine Male medicine.medical_specialty CIENCIAS MÉDICAS Y DE LA SALUD AMBIGUOUS GENITALIA Mutation Missense 030209 endocrinology & metabolism Medicina Clínica Consanguinity Disease Biology Gene mutation 03 medical and health sciences Middle East 0302 clinical medicine Africa Northern Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency Internal medicine medicine Missense mutation Humans Congenital adrenal hyperplasia Steroid 11-beta-hydroxylase Gonadal Steroid Hormones Multidisciplinary Adrenal Hyperplasia Congenital CLASSIC CAH medicine.disease Pedigree 030104 developmental biology Endocrinology PNAS Plus STEROID HORMONES Sex steroid Steroid 11-beta-Hydroxylase Female Medicina Critica y de Emergencia |
| Popis: | Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH. Fil: Khattab, Ahmed. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Haider, Shozeb. University College London; Estados Unidos Fil: Kumar, Ameet. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Dhawan, Samarth. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Alam, Dauood. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Romero, Raquel. University College London; Estados Unidos Fil: Burns, James. University College London; Estados Unidos Fil: Li, Di. University College London; Estados Unidos Fil: Estatico, Jessica. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Rahi, Simran. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Fatima, Saleel. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Alzahrani, Ali. King Faisal Specialist Hospital And Research Centre; Arabia Saudita Fil: Hafez, Mona. Cairo University; Egipto Fil: Musa, Noha. Cairo University; Egipto Fil: Azar, Maryam Razzghy. Iran University Of Medical Sciences; Irán Fil: Khaloul, Najoua. Hopital Farhat Hached Sousse; Túnez Fil: Gribaa, Moez. Hopital Farhat Hached Sousse; Túnez Fil: Saad, Ali. Hopital Farhat Hached Sousse; Túnez Fil: Charfeddine, Ilhem Ben. Hopital Farhat Hached Sousse; Túnez Fil: De Mendonça, Berenice Bilharinho. Universidade de Sao Paulo; Brasil Fil: Belgorosky, Alicia. Hospital de Pediatria Samic Prof. Dr. Juan P. Garrahan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Dumic, Katja. University Of Zagreb. School Of Medicine; Croacia Fil: Dumic, Miroslav. University Of Zagreb. School Of Medicine; Croacia Fil: Aisenberg, Javier. Hackensack University Medical Center; Estados Unidos Fil: Kandemir, Nurgun. Hacettepe Universitesi; Turquía Fil: Alikasifoglu, Ayfer. Hacettepe Universitesi; Turquía Fil: Ozon, Alev. Hacettepe Universitesi; Turquía Fil: Gonc, Nazli. Hacettepe Universitesi; Turquía Fil: Cheng, Tina. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Kuhnle Krahl, Ursula. University of Munich; Alemania Fil: Cappa, Marco. Ospedale Pediatrico Bambino Gesu; Italia Fil: Holterhus, Paul-Martin. Universitatsklinikum Schleswig-Holstein; Alemania Fil: Nour, Munier A.. University of Saskatchewan; Canadá Fil: Pacaud, Daniele. University of Calgary; Canadá Fil: Holtzman, Assaf. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Li, Sun. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Zaidi, Mone. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Yuen, Tony. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: New, Maria I.. Icahn School Of Medicine At Mount Sinai; Estados Unidos |
| Databáze: | OpenAIRE |
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