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One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver-Russell syndrome.
Meyer, Robert; Begemann, Matthias; Hübner, Christian Thomas; Dey, Daniela; Kuechler, Alma; Elgizouli, Magdeldin; Schara, Ulrike; Ambrozaityte, Laima; Burnyte, Birute; Schröder, Carmen; Kenawy, Asmaa; Kroisel, Peter; Demuth, Stephanie; Fekete, Gyorgy; Opladen, Thomas; Elbracht, Miriam; Eggermann, Thomas.
Afiliação
  • Meyer R; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
  • Begemann M; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
  • Hübner CT; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
  • Dey D; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
  • Kuechler A; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • Elgizouli M; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
  • Schara U; Department of Neuropediatrics, University Children's Hospital, University Duisburg-Essen, Essen, Germany.
  • Ambrozaityte L; Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
  • Burnyte B; Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
  • Schröder C; Zentrum Für Kinder- Und Jugendmedizin, Abt. Allgemeine Pädiatrie, Universitätsmedizin Greifswald, Greifswald, Germany.
  • Kenawy A; Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
  • Kroisel P; Institute of Human Genetics, Graz, Austria.
  • Demuth S; Praxis Für Humangenetik, Erfurt, Germany.
  • Fekete G; II. Department of Pediatrics, Semmelweis University, Budapest, Hungary.
  • Opladen T; Division for Child Neurology and Metabolic Medicine, University Children's Hospital Heidelberg, Heidelberg, Germany.
  • Elbracht M; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
  • Eggermann T; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. teggermann@ukaachen.de.
Orphanet J Rare Dis ; 16(1): 42, 2021 01 22.
Article em En | MEDLINE | ID: mdl-33482836
ABSTRACT

BACKGROUND:

Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented. MAIN BODY We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS.

CONCLUSIONS:

WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome de Silver-Russell Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome de Silver-Russell Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article