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DNA Methylation Profiling and Genomic Analysis in 20 Children with Short Stature Who Were Born Small for Gestational Age.
Peeters, Silke; Declerck, Ken; Thomas, Muriel; Boudin, Eveline; Beckers, Dominique; Chivu, Olimpia; Heinrichs, Claudine; Devriendt, Koenraad; de Zegher, Francis; Van Hul, Wim; Vanden Berghe, Wim; De Schepper, Jean; Rooman, Raoul; Mortier, Geert.
Afiliação
  • Peeters S; Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
  • Declerck K; Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
  • Thomas M; Belgian Society for Pediatric Endocrinology and Diabetology, Brussels, Belgium.
  • Boudin E; Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
  • Beckers D; Unité d'Endocrinologie Pédiatrique, CHU Namur, Université catholique de Louvain, Yvoir, Belgium and Department of Pediatrics, University Hospital Leuven, Leuven, Belgium.
  • Chivu O; Department of Pediatrics, Clinique de l'Espérance, Saint-Nicolas, Belgium.
  • Heinrichs C; Paediatric Endocrinology Unit, Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Brussels, Belgium.
  • Devriendt K; Center for Human Genetics, University of Leuven and the University Hospital Leuven, Leuven, Belgium.
  • de Zegher F; Department of Development & Regeneration, University of Leuven, Leuven, Belgium.
  • Van Hul W; Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
  • Vanden Berghe W; Laboratory of Protein Chemistry, Proteomics and Epigenetic Signalling (PPES), Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
  • De Schepper J; Department of Pediatrics, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel, Brussels, Belgium and Department of Pediatrics, Universitair Ziekenhuis Gent, Ghent, Belgium.
  • Rooman R; PendoCon bvba, Putte, Belgium.
  • Mortier G; Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Article em En | MEDLINE | ID: mdl-32685970
PURPOSE: In a significant proportion of children born small for gestational age (SGA) with failure of catch-up growth, the etiology of short stature remains unclear after routine diagnostic workup. We wanted to investigate if extensive analysis of the (epi)genome can unravel the cause of growth failure in a significant portion of these children. PATIENTS AND METHODS: Twenty SGA children treated with GH because of short stature were selected from the BELGROW database of the Belgian Society for Pediatric Endocrinology and Diabetology for exome sequencing, single-nucleotide polymorphism (SNP) array and genome-wide methylation analysis to identify the (epi)genetic cause. First-year response to GH was compared with the response of SGA patients in the KIGS database. RESULTS: We identified (likely) pathogenic variants in 4 children (from 3 families) using exome sequencing and found pathogenic copy number variants in 2 probands using SNP array. In a child harboring a NSD1-containing microduplication, we identified a DNA methylation signature that is opposite to the genome-wide DNA methylation signature of Sotos syndrome. Moreover, we observed multilocus imprinting disturbances in 2 children in whom no other genomic alteration could be identified. Five of 6 children with a genetic diagnosis had an "above average" response to GH. CONCLUSIONS: The study indicates that a more advanced approach with deep genotyping can unravel unexpected (epi)genomic alterations in SGA children with persistent growth failure. Most SGA children with a genetic diagnosis had a good response to GH treatment.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Recém-Nascido Pequeno para a Idade Gestacional / Metilação de DNA / Doenças do Recém-Nascido Limite: Female / Humans / Male / Newborn Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Recém-Nascido Pequeno para a Idade Gestacional / Metilação de DNA / Doenças do Recém-Nascido Limite: Female / Humans / Male / Newborn Idioma: En Ano de publicação: 2020 Tipo de documento: Article