1. Molecular Karyotyping as a Relevant Diagnostic Tool in Children with Growth Retardation with Silver-Russell Features
- Author
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Thomas Eggermann, Matthias Begemann, Anna Jauch, Bernd Denecke, Michael Baudis, Ute Moog, Barbara Oehl-Jaschkowitz, Klaus Zerres, Peter Michael Kroisel, Bernd Schulze, Peter Blümel, Nadina Ortiz Brüchle, Sabrina Spengler, Gisela Raabe-Meyer, Christiane Spaich, University of Zurich, and Spengler, Sabrina
- Subjects
Genetic Markers ,Male ,Biology ,Polymorphism, Single Nucleotide ,parasitic diseases ,medicine ,Humans ,2735 Pediatrics, Perinatology and Child Health ,Copy-number variation ,Child ,Growth Disorders ,Oligonucleotide Array Sequence Analysis ,Chromosome Aberrations ,Chromosome 7 (human) ,Genetics ,medicine.diagnostic_test ,Chromosomes, Human, Pair 11 ,Silver–Russell syndrome ,Infant ,Karyotype ,medicine.disease ,Phenotype ,10124 Institute of Molecular Life Sciences ,Silver-Russell Syndrome ,Genetic marker ,Child, Preschool ,Karyotyping ,Mutation ,Pediatrics, Perinatology and Child Health ,570 Life sciences ,biology ,Female ,Chromosome Deletion ,Chromosomes, Human, Pair 7 ,Fluorescence in situ hybridization ,SNP array - Abstract
Objective To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes. Study design We performed molecular karyotyping in 41 patients with SRS or SRS-like features without known chromosome 7 and 11 defects using the Affymetrix SNP Array 6.0 system (Affymetrix, High Wycombe, United Kingdom). Results In 8 patients, pathogenic copy number variations with sizes ranging from 672 kb to 9.158 Mb were identified. The deletions in 1q21, 15q26, 17p13, and 22q11 were associated with known microdeletion syndromes with overlapping features with SRS. The duplications in 22q13 and Xq25q27 represent unique novel copy number variations but have an obvious influence on the phenotype. In 5 additional patients, the pathogenetic relevance of the detected variants remained unclear. Conclusion Pathogenic submicroscopic imbalances were detectable in a significant proportion of patients with short stature and features reminiscent of SRS. Therefore, molecular karyotyping should be implemented in routine diagnostics for growth-retarded patients with even slight dysmorphisms suggestive for SRS.
- Published
- 2012