Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author 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
MENDONCA, Berenice Bilharinho de FMUSP-HC
BELGOROSKY, Alicia
DUMIC, Katja
DUMIC, Miroslav
AISENBERG, Javier
KANDEMIR, Nurgun
ALIKASIFOGLU, Ayfer
OZON, Alev
GONC, Nazli
CHENG, Tina
KUHNLE-KRAHL, Ursula
CAPPA, Marco
HOLTERHUS, Paul-Martin
NOUR, Munier A.
PACAUD, Daniele
HOLTZMAN, Assaf
LI, Sun
ZAIDI, Mone
YUEN, Tony
NEW, Maria I.
dc.date.issued 2017
dc.identifier.citation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.114, n.10, p.E1933-E1940, 2017
dc.identifier.issn 0027-8424
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/21237
dc.description.abstract Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11 beta-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 11 beta-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 11 beta-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 11 beta-hydroxylase deficiency CAH.
dc.description.sponsorship · Maria I. New Children Hormone Foundation
· NIH [DK80459, AG40132, AR06592, AR06066]
· University College London Excellence fellowship
dc.language.iso eng
dc.publisher NATL ACAD SCIENCES
dc.relation.ispartof Proceedings of the National Academy of Sciences of the United States of America
dc.rights restrictedAccess
dc.subject steroid hormones; missense mutations; classic CAH; ambiguous genitalia
dc.subject.other cyp11b1 gene; 21-hydroxylase deficiency; 11-hydroxylase deficiency; consanguineous marriage; hydroxylase deficiency; prenatal-diagnosis; point mutations; high-frequency; simulations; proteins
dc.title Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency
dc.type article
dc.rights.holder Copyright NATL ACAD SCIENCES
dc.description.group LIM/42
dc.identifier.doi 10.1073/pnas.1621082114
dc.identifier.pmid 28228528
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author MENDONCA, Berenice Bilharinho de:FM:MCM
hcfmusp.author.external · KHATTAB, Ahmed:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· HAIDER, Shozeb:UCL, Sch Pharm, London WC1N 4AX, England
· KUMAR, Ameet:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· DHAWAN, Samarth:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· ALAM, Dauood:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· ROMERO, Raquel:UCL, Sch Pharm, London WC1N 4AX, England
· BURNS, James:UCL, Sch Pharm, London WC1N 4AX, England
· LI, Di:UCL, Sch Pharm, London WC1N 4AX, England
· ESTATICO, Jessica:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· RAHI, Simran:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· FATIMA, Saleel:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· ALZAHRANI, Ali:King Faisal Specialist Hosp & Res Ctr, Riyadh 12713, Saudi Arabia
· HAFEZ, Mona:Cairo Univ, Diabet Endocrine & Metab Pediat Unit, Dept Pediat, Cairo 11617, Egypt
· MUSA, Noha:Cairo Univ, Diabet Endocrine & Metab Pediat Unit, Dept Pediat, Cairo 11617, Egypt
· AZAR, Maryam Razzghy:Iran Univ, Med Sci, Ali Asghar Childrens Hosp, Tehran 10000, Iran
· KHALOUL, Najoua:Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Biol Reprod, Sousse, Tunisia
· GRIBAA, Moez:Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Biol Reprod, Sousse, Tunisia
· SAAD, Ali:Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Biol Reprod, Sousse, Tunisia
· CHARFEDDINE, Ilhem Ben:Farhat Hached Univ Hosp, Lab Human Cytogenet Mol Genet & Biol Reprod, Sousse, Tunisia
· BELGOROSKY, Alicia:Garrahan Pediat Hosp, RA-1881 Buenos Aires, DF, Argentina
· DUMIC, Katja:Univ Hosp Ctr Zagreb, Zagreb 10000, Croatia
· DUMIC, Miroslav:Univ Hosp Ctr Zagreb, Zagreb 10000, Croatia
· AISENBERG, Javier:Hackensack Univ, Med Ctr, Pediat Endocrinol & Diabet Med, Hackensack, NJ 07601 USA
· KANDEMIR, Nurgun:Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey
· ALIKASIFOGLU, Ayfer:Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey
· OZON, Alev:Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey
· GONC, Nazli:Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey
· CHENG, Tina:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· KUHNLE-KRAHL, Ursula:Univ Munich, Childrens Hosp, D-80539 Munich, Germany
· CAPPA, Marco:Bambino Gesu Pediat Hosp, I-00146 Rome, Italy
· HOLTERHUS, Paul-Martin:Univ Hosp Schleswig Holstein, Dept Pediat, D-24105 Kiel, Germany
· NOUR, Munier A.:Univ Saskatchewan, Coll Med, Dept Pediat, Saskatoon, SK S7N 0W8, Canada
· PACAUD, Daniele:Univ Calgary, Dept Pediat, Calgary, AB T3B 6A8, Canada
· HOLTZMAN, Assaf:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· LI, Sun:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· ZAIDI, Mone:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· YUEN, Tony:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
· NEW, Maria I.:Icahn Sch Med Mt Sinai, Dept Pediat, Div Adrenal Steroid Disorders, New York, NY 10029 USA; Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA
hcfmusp.origem.id 2-s2.0-85014711618
hcfmusp.origem.id WOS:000395511400020
hcfmusp.publisher.city WASHINGTON
hcfmusp.publisher.country USA
hcfmusp.relation.reference · Al-Abdulkareem AA, 1998, J COMMUN HEALTH, V23, P75, DOI 10.1023/A:1018727005707
· Alper OM, 2004, ANN GENET-PARIS, V47, P129, DOI 10.1016/j.anngen.2003.09.001
· Alqahtani MA, 2015, INT J ENDOCRINOL, DOI 10.1155/2015/595164
· Ben Charfeddine I, 2012, GEN COMP ENDOCR, V175, P514, DOI 10.1016/j.ygcen.2011.12.017
· Bin-Abbas B, 2014, ENDOCR PRACT, V20, pE191, DOI 10.4158/EP14179.CR
· Cerame BI, 1999, J CLIN ENDOCR METAB, V84, P3129, DOI 10.1210/jc.84.9.3129
· CHUA SC, 1987, P NATL ACAD SCI USA, V84, P7193, DOI 10.1073/pnas.84.20.7193
· Cojocaru V, 2011, PLOS COMPUT BIOL, V7, DOI 10.1371/journal.pcbi.1002152
· CURNOW KM, 1993, P NATL ACAD SCI USA, V90, P4552, DOI 10.1073/pnas.90.10.4552
· Dumic K, 2014, INT J ENDOCRINOL, DOI 10.1155/2014/185974
· Dumic K, 2010, EUR J PEDIATR, V169, P891, DOI 10.1007/s00431-009-1110-1
· HAFEZ M, 1983, J MED GENET, V20, P58, DOI 10.1136/jmg.20.1.58
· Haider S, 2013, P NATL ACAD SCI USA, V110, P2605, DOI 10.1073/pnas.1221133110
· Joehrer K, 1997, HUM MOL GENET, V6, P1829, DOI 10.1093/hmg/6.11.1829
· Kandemir N, 1997, ACTA PAEDIATR, V86, P22, DOI 10.1111/j.1651-2227.1997.tb08824.x
· Krone N, 2005, J CLIN ENDOCR METAB, V90, P3724, DOI 10.1210/jc.2005-0089
· Krone N, 2006, J CLIN ENDOCR METAB, V91, P2682, DOI 10.1210/ja.2006-0209
· Laskowski RA, 1996, J BIOMOL NMR, V8, P477, DOI 10.1007/BF00228148
· Mancenido D, 2014, GENETIC STEROID DISORDERS, P53, DOI 10.1016/B978-0-12-416006-4.00004-1
· Marrink SJ, 2007, J PHYS CHEM B, V111, P7812, DOI 10.1021/jp071097f
· Motaghedi R, 2005, J PEDIATR ENDOCR MET, V18, P133
· New MI, 2014, GENETIC STEROID DISORDERS, P29, DOI 10.1016/B978-0-12-416006-4.00003-X
· New MI, 2013, P NATL ACAD SCI USA, V110, P2611, DOI 10.1073/pnas.1300057110
· Pronk S, 2013, BIOINFORMATICS, V29, P845, DOI 10.1093/bioinformatics/btt055
· Rashin AA, 1997, PROTEIN SCI, V6, P2143
· ROSLER A, 1992, AM J MED GENET, V42, P827, DOI 10.1002/ajmg.1320420617
· Saadat M, 2004, ANN HUM BIOL, V31, P263, DOI 10.1080/03014460310001652211
· Sievers F., 2014, CURR PROTOC BIOINFOR, V48, P3, DOI 10.1002/0471250953.BI0313S48
· Sievers F, 2014, METHODS MOL BIOL, V1079, P105, DOI 10.1007/978-1-62703-646-7_6
· Soardi FC, 2009, J CLIN ENDOCR METAB, V94, P3481, DOI 10.1210/jc.2008-2521
· SPEISER PW, 1985, AM J HUM GENET, V37, P650
· Stansfeld PJ, 2011, J CHEM THEORY COMPUT, V7, P1157, DOI 10.1021/ct100569y
· Tadmouri Ghazi O, 2009, Reprod Health, V6, P17, DOI 10.1186/1742-4755-6-17
· Webb B, 2016, CURR PROTOC BIOINFOR, V54, DOI 10.1186/1471-2105-11-568
· White PC, 2014, GENETIC STEROID DISORDERS, P71, DOI 10.1016/B978-0-12-416006-4.00006-5
· Wiederstein M, 2007, NUCLEIC ACIDS RES, V35, pW407, DOI 10.1093/nar/gkm290
· ZACHMANN M, 1983, J CLIN ENDOCR METAB, V56, P222
dc.description.index MEDLINE
hcfmusp.citation.scopus 26
hcfmusp.citation.wos 22
hcfmusp.affiliation.country Brasil
hcfmusp.affiliation.country Inglaterra
hcfmusp.affiliation.country Árabia Saudita
hcfmusp.affiliation.country Egito
hcfmusp.affiliation.country Irã
hcfmusp.affiliation.country Tunísia
hcfmusp.affiliation.country Estados Unidos
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