One test for all: whole exome sequencing signifcantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome /

Robert Meyer; Matthias Begemann; Christian Thomas Hübner; Daniela Dey; Alma Kuechler; Magdeldin Elgizouli; Ulrike Schara; Laima Ambrozaitytė; Birutė Burnytė; Carmen Schröder; Asmaa Kenawy; Peter Kroisel; Stephanie Demuth; Gyorgy Fekete; Thomas Opladen; Miriam Elbracht; Thomas Eggermann

doi:10.1186/s13023-021-01683-x

Title	One test for all: whole exome sequencing signifcantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome /
Authors	Meyer, Robert ; Begemann, Matthias ; Hübner, Christian Thomas ; Dey, Daniela ; Kuechler, Alma ; Elgizouli, Magdeldin ; Schara, Ulrike ; Ambrozaitytė, Laima ; Burnytė, Birutė ; Schröder, Carmen ; Kenawy, Asmaa ; Kroisel, Peter ; Demuth, Stephanie ; Fekete, Gyorgy ; Opladen, Thomas ; Elbracht, Miriam ; Eggermann, Thomas
DOI	10.1186/s13023-021-01683-x
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Is Part of	Orphanet journal of rare diseases.. London : BioMed Central Ltd.. 2021, vol. 16, art. no. 42, p. [1-10].. eISSN 1750-1172
Keywords [eng]	Silver–Russell syndrome ; next generation sequencing ; diagnostic detection rate ; whole exome sequencing ; targeted multigene panel NGS
Abstract [eng]	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 chromo-some 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.
Published	London : BioMed Central Ltd
Type	Journal article
Language	English
Publication date	2021
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„One test for all: whole exome sequencing signifcantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome /“