ARMC5 Mutations Are a Frequent Cause of Primary Macronodular Adrenal Hyperplasia

Show simple item record

dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP ALENCAR, Guilherme Asmar FMUSP-HC
LERARIO, Antonio Marcondes FMUSP-HC
NISHI, Mirian Yumie FMUSP-HC
MARIANI, Beatriz Marinho de Paula FMUSP-HC
ALMEIDA, Madson Queiroz FMUSP-HC
HAMET, Pavel
BOURDEAU, Isabelle
ZERBINI, Maria Claudia Nogueira FMUSP-HC
PEREIRA, Maria Adelaide Albergaria FMUSP-HC
GOMES, Gilberto Carlos FMUSP-HC
ROCHA, Manoel de Souza FMUSP-HC
MENDONCA, Berenice Bilharinho FMUSP-HC
FRAGOSO, Maria Candida Barisson Villares FMUSP-HC 2014
dc.identifier.citation JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.99, n.8, p.E1501-E1509, 2014
dc.identifier.issn 0021-972X
dc.description.abstract Context: Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, usually characterized by functioning adrenal macronodules and increased cortisol production. Familial clustering of PMAH has been described, suggesting an inherited genetic cause for this condition. Objective: The aim of the present study was to identify the gene responsible for familial PMAH. Patients and Methods: Forty-seven individuals of a Brazilian family with PMAH were evaluated. A single-nucleotide polymorphism-based genome-wide linkage analysis followed by whole-exome sequencing were then performed in selected family members. Additionally, 29 other patients with PMAH and 125 randomly selected healthy individuals were studied to validate the genetic findings. Moreover, PMAH tissue was also analyzed through whole-exome sequencing, conventional sequencing, and microsatellite analysis. Results: A heterozygous germline variant in the ARMC5 gene (p.Leu365Pro) was identified by whole-exome sequencing in a candidate genomic region (16p11.2). Subsequently, the same variant was confirmed by conventional sequencing in all 16 affected family members. The variant was predicted to be damaging by in silico methods and was not found in available online databases or in the 125 selected healthy individuals. Seven additional ARMC5 variants were subsequently identified in 5 of 21 patients with apparently sporadic PMAH and in 2 of 3 families with the disease. Further molecular analysis identified a somatic mutational event in 4 patients whose adrenal tissue was available. Conclusions: Inherited autosomal dominant mutations in the ARMC5 gene are a frequent cause of PMAH. Biallelic inactivation of ARMC5 is consistent with its role as a potential tumor suppressor gene.
dc.description.sponsorship · Sao Paulo Research Foundation (FAPESP) [2010/12702-1]
· Brazilian fostering agency Coordination for the Improvement of Higher Education Personnel
· genome-wide linkage study platform at Centre Hospitalier de l'Universite de Montreal research center
dc.language.iso eng
dc.publisher ENDOCRINE SOC
dc.relation.ispartof Journal of Clinical Endocrinology & Metabolism
dc.rights restrictedAccess
dc.subject.other independent cushings-syndrome; gastric-inhibitory polypeptide; protein function; vasopressin; glands; receptors; corticotropin; heterogeneity; expression; secretion
dc.title ARMC5 Mutations Are a Frequent Cause of Primary Macronodular Adrenal Hyperplasia
dc.type article
dc.rights.holder Copyright ENDOCRINE SOC LIM/42 LIM/14
dc.identifier.doi 10.1210/jc.2013-4237
dc.type.category original article
dc.type.version publishedVersion ALENCAR, Guilherme Asmar:FM: LERARIO, Antonio Marcondes:HC:LIM/42 NISHI, Mirian Yumie:HC:LIM/42 MARIANI, Beatriz Marinho de Paula:FM: ALMEIDA, Madson Queiroz:HC:LIM/42 ZERBINI, Maria Claudia Nogueira:FM:MPT PEREIRA, Maria Adelaide Albergaria:HC:ICHC GOMES, Gilberto Carlos:HC:INRAD ROCHA, Manoel de Souza:FM:MDR CHAMBO, Jose Luis:HC:ICHC MENDONCA, Berenice Bilharinho:FM:MCM FRAGOSO, Maria Candida Barisson Villares:HC:LIM/42 · TREMBLAY, Johanne:Univ Montreal, Ctr Hosp, Dept Med, Montreal, PQ H2W 1T8, Canada
· HAMET, Pavel:Univ Montreal, Ctr Hosp, Dept Med, Montreal, PQ H2W 1T8, Canada
· BOURDEAU, Isabelle:Univ Montreal, Ctr Hosp, Dept Med, Montreal, PQ H2W 1T8, Canada
· LACROIX, Andre:Univ Montreal, Ctr Hosp, Dept Med, Montreal, PQ H2W 1T8, Canada 2-s2.0-84905828393 WOS:000342341200015 WASHINGTON USA
hcfmusp.relation.reference · Adzhubei I, 2013, CURR PROTOC HUM GENE, V7, P20
· Almeida MQ, 2011, J CLIN ENDOCR METAB, V96, pE728, DOI 10.1210/jc.2010-2420
· Assie G, 2013, NEW ENGL J MED, V369, P2105, DOI 10.1056/NEJMoa1304603
· Berthon A, 2012, MOL CELL ENDOCRINOL, V351, P87, DOI 10.1016/j.mce.2011.09.009
· Bourdeau I, 2004, ONCOGENE, V23, P1575, DOI 10.1038/sj.onc.1207277
· Bourdeau I, 2007, 89 ANN M END SOC TOR, P148
· Bromberg Y, 2008, BIOINFORMATICS, V24, P2397, DOI 10.1093/bioinformatics/btn435
· FINDLAY JC, 1993, J CLIN ENDOCR METAB, V76, P189, DOI 10.1210/jc.76.1.189
· Fragoso MCBV, 2003, J CLIN ENDOCR METAB, V88, P2147, DOI 10.1210/jc.2002-021362
· Gagliardi L, 2009, CLIN ENDOCRINOL, V70, P883, DOI 10.1111/j.1365-2265.2008.03471.x
· Groen EJ, 2008, ANN SURG ONCOL, V15, P2439, DOI 10.1245/s10434-008-9981-3
· Hsiao HP, 2009, J CLIN ENDOCR METAB, V94, P2930, DOI 10.1210/jc.2009-0516
· Imohl M, 2002, MED KLIN, V97, P747, DOI 10.1007/s00063-002-1220-2
· Lacroix A, 2010, CLIN ENDOCRINOL, V73, P1, DOI 10.1111/j.1365-2265.2009.03689.x
· LACROIX A, 1992, NEW ENGL J MED, V327, P974, DOI 10.1056/NEJM199210013271402
· Lacroix A, 2009, BEST PRACT RES CL EN, V23, P245, DOI 10.1016/j.beem.2008.10.011
· Lee S, 2005, CLIN ENDOCRINOL, V63, P625, DOI 10.1111/j.1365-2265.2005.02387.x
· Louiset E, 2013, NEW ENGL J MED, V369, P2115, DOI 10.1056/NEJMoa1215245
· Matyakhina L, 2005, J CLIN ENDOCR METAB, V90, P3773, DOI 10.1210/jc.2004-2377
· MILLER SA, 1988, NUCLEIC ACIDS RES, V16, P1215, DOI 10.1093/nar/16.3.1215
· Minami S, 1996, CLIN ENDOCRINOL, V44, P483, DOI 10.1046/j.1365-2265.1996.682504.x
· Miyamura N, 2002, ENDOCRINE, V19, P319, DOI 10.1385/ENDO:19:3:319
· Newell-Price J, 2006, LANCET, V367, P1605, DOI 10.1016/S0140-6736(06)68699-6
· Ng PC, 2003, NUCLEIC ACIDS RES, V31, P3812, DOI 10.1093/nar/gkg509
· Nies C, 2002, EXP CLIN ENDOCR DIAB, V110, P277, DOI 10.1055/s-2002-34590
· Oheda T, 1995, FOLIA ENDOCRINOL, V71, P416
· REZNIK Y, 1992, NEW ENGL J MED, V327, P981, DOI 10.1056/NEJM199210013271403
· Schwarz JM, 2010, NAT METHODS, V7, P575, DOI 10.1038/nmeth0810-575
· SKOGSEID B, 1992, J CLIN ENDOCR METAB, V75, P76, DOI 10.1210/jc.75.1.76
· Sohaib SA, 1999, AM J ROENTGENOL, V172, P997
· Someya T, 1996, FOLIA ENDOCRINOL, V72, P762
· Stratakis CA, 2007, NAT CLIN PRACT ENDOC, V3, P748, DOI 10.1038/ncpendmet0648
· Swain JM, 1998, ARCH SURG-CHICAGO, V133, P541, DOI 10.1001/archsurg.133.5.541
· Swords FM, 2002, MOL ENDOCRINOL, V16, P2746, DOI 10.1210/me.2002-0099
· Tewari R, 2010, TRENDS CELL BIOL, V20, P470, DOI 10.1016/j.tcb.2010.05.003
· Vernooij MW, 2007, NEW ENGL J MED, V357, P1821, DOI 10.1056/NEJMoa070972
· Vezzosi D, 2007, EUR J ENDOCRINOL, V156, P21, DOI 10.1530/eje.1.02324
· VINCENT JM, 1994, CLIN RADIOL, V49, P453, DOI 10.1016/S0009-9260(05)81739-8
· Watson TD, 2007, RADIOLOGY, V244, P923
dc.description.index MEDLINE
dc.identifier.eissn 1945-7197
hcfmusp.citation.scopus 66
hcfmusp.citation.wos 53 Brasil Canadá

Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


My Account