Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.

Autor: Pfundt R; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Del Rosario M; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Vissers LELM; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Kwint MP; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Janssen IM; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., de Leeuw N; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Yntema HG; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Nelen MR; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Lugtenberg D; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Kamsteeg EJ; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Wieskamp N; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Stegmann APA; Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands., Stevens SJC; Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands., Rodenburg RJT; Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands.; Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands., Simons A; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Mensenkamp AR; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Rinne T; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Gilissen C; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands., Scheffer H; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands., Veltman JA Prof Dr; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Clinical Genetics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands., Hehir-Kwa JY; Department of Human Genetics, Donders Institute, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2017 Jun; Vol. 19 (6), pp. 667-675. Date of Electronic Publication: 2016 Oct 27.
DOI: 10.1038/gim.2016.163
Abstrakt: Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10-20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test.
Methods: We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting.
Results: In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to -5.8% per disorder).
Conclusions: This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics.Genet Med advance online publication 27 October 2016.
Databáze: MEDLINE
Externí odkaz: