Diagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature

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dc.creatorNathalia Liberatoscioli Menezesandrade
dc.creatorMicheline a r Souza
dc.creatorBruna l Freire
dc.creatorAna c v Krepischi
dc.creatorCarlos Alberto Longui
dc.creatorAntonio Marcondes Lerario
dc.creatorIvo j p Arnhold
dc.creatorAlexander a l Jorge
dc.creatorGabriela Andrade Vasques
dc.creatorMariana Ferreira de Assis Funari
dc.creatorAlexsandra Christianne Malaquias
dc.creatorPaulo Ferrez Collett-solberg
dc.creatorNathália Lisboa Rosa Almeida Gomes
dc.creatorRenata Scalco
dc.creatorNaiara Castelo Branco Dantas
dc.creatorRaissa c Rezende
dc.creatorAngelica m f p Tiburcio
dc.date.accessioned2023-11-06T22:12:40Z
dc.date.accessioned2025-09-08T23:02:44Z
dc.date.available2023-11-06T22:12:40Z
dc.date.issued2022
dc.format.mimetypepdf
dc.identifier.doi10.1530/ec-22-0214
dc.identifier.issn20493614
dc.identifier.urihttps://hdl.handle.net/1843/60543
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofEndocrine Connections
dc.rightsAcesso Aberto
dc.subjectBody Height
dc.subjectGenetic Association Studies
dc.subjectSuppression, Genetic
dc.subject.otherIdiopathic short stature
dc.subject.othermultigene sequencing analysis
dc.subject.otherGenetic
dc.subject.otherSuppression, Genetic
dc.titleDiagnostic yield of a multigene sequencing approach in children classified as idiopathic short stature
dc.typeArtigo de periódico
local.citation.epage10
local.citation.issue12
local.citation.spage1
local.citation.volume11
local.description.resumoObjective: Most children with short stature remain without an etiologic diagnosis after extensive clinical and laboratory evaluation and are classified as idiopathic short stature (ISS). This study aimed to determine the diagnostic yield of a multigene analysis in children classified as ISS.Design and methods: We selected 102 children with ISS and performed the genetic analysis as part of the initial investigation. We developed customized targeted panel sequencing, including all genes already implicated in the isolated short-stature phenotype. Rare and deleterious single nucleotide or copy number variants were assessed by bioinformatic tools.Results: We identified 20 heterozygous pathogenic (P) or likely pathogenic (LP) genetic variants in 17 of 102 patients (diagnostic yield = 16.7%). Three patients had more than one P/LP genetic alteration. Most of the findings were in genes associated with the growth plate differentiation: IHH (n  = 4), SHOX (n  = 3), FGFR3 (n  = 2), NPR2 (n  = 2), ACAN(n  = 2), and COL2A1 (n  = 1) or involved in the RAS/MAPK pathway: NF1 (n  = 2), PTPN11(n  = 1), CBL (n  = 1), and BRAF (n  = 1). None of these patients had clinical findings to guide a candidate gene approach. The diagnostic yield was higher among children with severe short stature (35% vs 12.2% for height SDS ≤ or > −3; P = 0.034). The genetic diagnosis had an impact on clinical management for four children.Conclusion: A multigene sequencing approach can determine the genetic etiology of short stature in up to one in six children with ISS, removing the term idiopathic from their clinical classification.
local.publisher.countryBrasil
local.publisher.departmentMED - DEPARTAMENTO DE CLÍNICA MÉDICA
local.publisher.initialsUFMG
local.url.externahttps://doi.org/10.1530/EC-22-0214

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