Structural and sequence variants in patients with Silver-Russell syndrome or similar features—Curation of a disease database
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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.
Original language | English |
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Journal | Human Mutation |
Volume | 39 |
Issue number | 3 |
Pages (from-to) | 345-364 |
Number of pages | 20 |
ISSN | 1059-7794 |
DOIs | |
Publication status | Published - 2018 |
- 11p15, growth retardation, LOVD database, methylation, NH-CSS, sequence variant, Silver-Russell syndrome, SRS, structural variant
Research areas
ID: 214518752