| Autor: |
Khattab, Ahmed, Haider, Shozeb, Kumar, Ameet, Dhawan, Samarth, Alam, Dauood, Romero, Raquel, Burns, James, Li, Di, Estatico, Jessica, Rahi, Simran, Fatima, Saleel, Alzahrani, Ali, Hafez, Mona, Musa, Noha, Azar, Maryam Razzghy, Khaloul, Najoua, Gribaa, Moez, Saad, Ali, Charfeddine, Ilhem Ben, de Mendonça, Berenice Bilharinho |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 3/7/2017, Vol. 114 Issue 10, pE1933-E1940, 8p |
| Abstrakt: |
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 identicalmutations. 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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