ATR-16 syndrome
| Autor: | Amanda Dixon-McIver, J. Traeger-Synodinos, Douglas R. Higgs, Shiwangini Kumar, Evie Maifoshie, Christian Babbs, Veronica J. Buckle, Paul Ooijevaar, Jill M. Brown, Cornelis L. Harteveld, Andrew O.M. Wilkie, Joanne Slater, Marjolein Kriek, Sharon W. Horsley |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Monosomy thalassemia DNA Copy Number Variations Thalassemia Genetic counseling CNV Ataxia Telangiectasia Mutated Proteins 030105 genetics & heredity Biology 03 medical and health sciences Chromosome 16 ATR16 alpha-Thalassemia Downregulation and upregulation Intellectual Disability Genetics medicine Humans Allele Gene Genetics (clinical) Genotype-Phenotype Correlations medicine.disease Phenotype developmental delay 030104 developmental biology Female Chromosome Deletion Chromosomes Human Pair 16 Gene Deletion |
| Zdroj: | Journal of Medical Genetics, 57(6), 414-421. BMJ PUBLISHING GROUP Journal of Medical Genetics |
| Popis: | BackgroundDeletions removing 100s–1000s kb of DNA, and variable numbers of poorly characterised genes, are often found in patients with a wide range of developmental abnormalities. In such cases, understanding the contribution of the deletion to an individual’s clinical phenotype is challenging.MethodsHere, as an example of this common phenomenon, we analysed 41 patients with simple deletions of ~177 to ~2000 kb affecting one allele of the well-characterised, gene dense, distal region of chromosome 16 (16p13.3), referred to as ATR-16 syndrome. We characterised deletion extents and screened for genetic background effects, telomere position effect and compensatory upregulation of hemizygous genes.ResultsWe find the risk of developmental and neurological abnormalities arises from much smaller distal chromosome 16 deletions (~400 kb) than previously reported. Beyond this, the severity of ATR-16 syndrome increases with deletion size, but there is no evidence that critical regions determine the developmental abnormalities associated with this disorder. Surprisingly, we find no evidence of telomere position effect or compensatory upregulation of hemizygous genes; however, genetic background effects substantially modify phenotypic abnormalities.ConclusionsUsing ATR-16 as a general model of disorders caused by CNVs, we show the degree to which individuals with contiguous gene syndromes are affected is not simply related to the number of genes deleted but depends on their genetic background. We also show there is no critical region defining the degree of phenotypic abnormalities in ATR-16 syndrome and this has important implications for genetic counselling. |
| Databáze: | OpenAIRE |
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