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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Human Mutation |
| Vol/bind | 39 |
| Udgave nummer | 3 |
| Sider (fra-til) | 345-364 |
| Antal sider | 20 |
| ISSN | 1059-7794 |
| DOI | |
| Status | Udgivet - 2018 |