Structural and sequence variants in patients with Silver‐Russell syndrome or similar features—Curation of a disease database |
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Authors: | Zeynep Tümer Julia Angélica López‐Hernández Irène Netchine Miriam Elbracht Karen Grønskov Lene Bjerring Gede Jana Sachwitz Johan T den Dunnen Thomas Eggermann |
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Institution: | 1. Applied Human Molecular Genetics, Kennedy Centre, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark;2. Human Genetics and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands;3. Sorbonne Universite, INSERM UMR_S 938, CDR Saint‐Antoine, Paris, France;4. APHP, Armand Trousseau Hospital, Pediatric Endocrinology, Paris, France;5. Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany |
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Abstract: | Silver‐Russell syndrome (SRS) is a clinically and molecularly heterogeneous disorder involving prenatal and postnatal growth retardation, and the term SRS‐like is broadly used to describe individuals with clinical features resembling SRS. The main molecular subgroups are loss of methylation of the distal imprinting control region (H19/IGF2:IG‐DMR) on 11p15.5 (50%) and maternal uniparental disomy of chromosome 7 (5%–10%). Through a comprehensive literature search, we identified 91 patients/families with various structural and small sequence variants, which were suggested as additional molecular defects leading to SRS/SRS‐like phenotypes. However, the molecular and phenotypic data of these patients were not standardized and therefore not comparable, rendering difficulties in phenotype–genotype comparisons. To overcome this challenge, we curated a disease database including (epi)genetic phenotypic data of these patients. The clinical features are scored according to the Netchine‐Harbison clinical scoring system (NH‐CSS), which has recently been accepted as standard by consensus. The structural and sequence variations are reviewed and where necessary redescribed according to recent recommendations. Our study provides a framework for both research and diagnostic purposes through facilitating a standardized comparison of (epi)genotypes with phenotypes of patients with structural/sequence variants. |
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Keywords: | 11p15 growth retardation LOVD database methylation NH‐CSS sequence variant Silver‐Russell syndrome SRS structural variant |
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