Publication:
Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort

dc.contributor.authorGüran, Tülay
dc.contributor.authorBuonocore, Federica
dc.contributor.authorSaka, Nurçin
dc.contributor.authorÖzbek, Mehmet Nuri
dc.contributor.authorAycan, Zehra
dc.contributor.authorBereket, Abdullah
dc.contributor.authorBaş, Firdevs
dc.contributor.authorDarcan, Sükran
dc.contributor.authorBideci, Aysun
dc.contributor.authorGüven, Ayla
dc.contributor.authorDemir, Korcan
dc.contributor.authorAkıncı, Ayşehan
dc.contributor.authorBüyükinan, Muammer
dc.contributor.authorAydın, Banu Küçükemre
dc.contributor.authorTuran, Serap
dc.contributor.authorAğladıoğlu, Sebahat Yılmaz
dc.contributor.authorAtay, Zeynep
dc.contributor.authorAbalı, Zehra Yavaş
dc.contributor.authorÇatlı, Gönül
dc.contributor.authorYüksel, Bilgin
dc.contributor.authorAkçay, Teoman
dc.contributor.authorYıldız, Metin
dc.contributor.authorÖzen, Samim
dc.contributor.authorDoger, Esra
dc.contributor.authorDemirbilek, Hüseyin
dc.contributor.authorUçar, Ahmet
dc.contributor.authorIşık, Emregül
dc.contributor.authorÖzhan, Bayaram
dc.contributor.authorBolu, Semih
dc.contributor.authorÖzgen, İlker Tolga
dc.contributor.authorSuntharalingham, Jenifer P.
dc.contributor.authorAchermann, John C.
dc.contributor.buuauthorTarım, Ömer
dc.contributor.departmentTıp Fakültesi
dc.contributor.departmentPediatrik Endokrinoloji ve Diyabet Ana Bilim Dalı
dc.contributor.scopusid6701427186
dc.date.accessioned2022-05-20T06:39:16Z
dc.date.available2022-05-20T06:39:16Z
dc.date.issued2016-01
dc.description.abstractContext: Primary adrenal insufficiency (PAI) is a life-threatening condition that is often due to monogenic causes in children. Although congenital adrenal hyperplasia occurs commonly, several other important molecular causes have been reported, often with overlapping clinical and biochemical features. The relative prevalence of these conditions is not known, but making a specific diagnosis can have important implications for management. Objective: The objective of the study was to investigate the clinical and molecular genetic characteristics of a nationwide cohort of children with PAI of unknown etiology. Design: A structured questionnaire was used to evaluate clinical, biochemical, and imaging data. Genetic analysis was performed using Haloplex capture and next-generation sequencing. Patients with congenital adrenal hyperplasia, adrenoleukodystrophy, autoimmune adrenal insufficiency, or obvious syndromic PAI were excluded. Setting: The study was conducted in 19 tertiary pediatric endocrinology clinics. Patients: Ninety-five children (48 females, aged 0-18 y, eight familial) with PAI of unknown etiology participated in the study. Results: A genetic diagnosis was obtained in 77 patients (81%). The range of etiologies was as follows: MC2R (n = 25), NR0B1 (n = 12), STAR (n = 11), CYP11A1 (n = 9), MRAP (n = 9), NNT (n = 7), ABCD1 (n = 2), NR5A1 (n = 1), and AAAS (n = 1). Recurrent mutations occurred in several genes, such as c.560delT in MC2R, p.R451W in CYP11A1, and c. IVS3ds + 1delG in MRAP. Several important clinical and molecular insights emerged. Conclusion: This is the largest nationwide study of the molecular genetics of childhood PAI undertaken. Achieving a molecular diagnosis in more than 80% of children has important translational impact for counseling families, presymptomatic diagnosis, personalized treatment (eg, mineralocorticoid replacement), predicting comorbidities (eg, neurological, puberty/fertility), and targeting clinical genetic testing in the future.
dc.description.sponsorshipTürk Pediatrik Endokrinoloji Araştırma Bursu- UPE-2014-2
dc.description.sponsorshipWellcome Trust/European Commission - 098513/Z/12/Z
dc.description.sponsorshipNational Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London
dc.description.sponsorshipEuropean Commission - PIEF-GA-2012-328959
dc.identifier.citationGüran, T. vd. (2016). "Rare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort". Journal of Clinical Endocrinology and Metabolism, 101(1), 283-291.
dc.identifier.endpage291
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.issue1
dc.identifier.pubmed26523528
dc.identifier.scopus2-s2.0-84954515152
dc.identifier.startpage283
dc.identifier.urihttps://doi.org/10.1210/jc.2015-3250
dc.identifier.urihttps://academic.oup.com/jcem/article/101/1/284/2806864?login=true
dc.identifier.urihttp://hdl.handle.net/11452/26538
dc.identifier.volume101
dc.identifier.wos000377212700036
dc.indexed.wosSCIE
dc.language.isoen
dc.publisherEndocrine Soc
dc.relation.collaborationYurt içi
dc.relation.collaborationYurt dışı
dc.relation.collaborationSanayi
dc.relation.journalJournal of Clinical Endocrinology and Metabolism
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectEndocrinology & metabolism
dc.subjectFamilial glucocorticoid deficiency
dc.subjectSteroidogenic factor-I
dc.subjectChain cleavage enzyme
dc.subjectKiller-cell deficiency
dc.subjectHypoplasia congenita
dc.subjectMissense mutations
dc.subjectActh receptor
dc.subjectDax-1 nrob1
dc.subjectFollow-up
dc.subjectCyp11A1
dc.subject.emtreeCholesterol monooxygenase (side chain cleaving)
dc.subject.emtreeCorticotropin
dc.subject.emtreeNicotinamide adenine dinucleotide (phosphate) transhydrogenase
dc.subject.emtreeDNA
dc.subject.emtreeAAAS gene
dc.subject.emtreeABCD1 gene
dc.subject.emtreeAdrenal insufficiency
dc.subject.emtreeArticle
dc.subject.emtreeChild
dc.subject.emtreeClinical evaluation
dc.subject.emtreeClinical feature
dc.subject.emtreeCohort analysis
dc.subject.emtreeCYP11A1 gene
dc.subject.emtreeFemale
dc.subject.emtreeFrameshift mutation
dc.subject.emtreeGene
dc.subject.emtreeGene deletion
dc.subject.emtreeGenetic analysis
dc.subject.emtreeGenetic procedures
dc.subject.emtreeGenetic variability
dc.subject.emtreeHigh throughput sequencing
dc.subject.emtreeHuman
dc.subject.emtreeMajor clinical study
dc.subject.emtreeMale
dc.subject.emtreeMC2R gene
dc.subject.emtreeMissense mutation
dc.subject.emtreeMolecular diagnosis
dc.subject.emtreeMRAP gene
dc.subject.emtreeMutational analysis
dc.subject.emtreeNewborn
dc.subject.emtreeNext generation sequencing
dc.subject.emtreeNNT gene
dc.subject.emtreeNonsense mutation
dc.subject.emtreeNR0B1 gene
dc.subject.emtreeNR5A1 gene
dc.subject.emtreePrimary adrenal insufficiency
dc.subject.emtreePriority journal
dc.subject.emtreeSequence capture
dc.subject.emtreeStructured questionnaire
dc.subject.emtreeAdolescent
dc.subject.emtreeAdrenal insufficiency
dc.subject.emtreeEpidemiology
dc.subject.emtreeGene expression
dc.subject.emtreeGenetic variation
dc.subject.emtreeGenetics
dc.subject.emtreeInfant
dc.subject.emtreeMutation
dc.subject.emtreeOnset age
dc.subject.emtreePreschool child
dc.subject.emtreeTurkey
dc.subject.meshAdolescent
dc.subject.meshAdrenal insufficiency
dc.subject.meshAge of onset
dc.subject.meshChild
dc.subject.meshChild, preschool
dc.subject.meshCohort studies
dc.subject.meshDNA
dc.subject.meshFemale
dc.subject.meshGene expression
dc.subject.meshGenetic variation
dc.subject.meshHumans
dc.subject.meshInfant
dc.subject.meshInfant, newborn
dc.subject.meshMale
dc.subject.meshMutation
dc.subject.meshTurkey
dc.subject.scopusAchalasia Addisonianism Alacrimia Syndrome; Melanocortin 2 Receptor; Alacrima
dc.subject.wosEndocrinology & metabolism
dc.titleRare causes of primary adrenal insufficiency: Genetic and clinical characterization of a large nationwide cohort
dc.typeArticle
dc.wos.quartileQ1
dspace.entity.typePublication
local.contributor.departmentTıp Fakültesi/Pediatrik Endokrinoloji ve Diyabet Ana Bilim Dalı
local.indexed.atPubMed
local.indexed.atWOS

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