Subject:
|
Biophysics DCN 2: Functional Neurogenomics DCN 3: Neuroinformatics EBP 2: Effective Hospital Care IGMD 3: Genomic disorders and inherited multi-system disorders NCMLS 6: Genetics and epigenetic pathways of disease ONCOL 1: Hereditary cancer and cancer-related syndromes ONCOL 3: Translational research UMCN 1.2: Molecular diagnosis, prognosis and monitoring UMCN 1.5: Interventional oncology EBP 2: Effective Hospital Care |
Organization:
|
Human Genetics Dermatology Cognitive Neuroscience Health Evidence |
Former Organization:
|
Medical Physics and Biophysics Epidemiology, Biostatistics & HTA
|
Journal title:
|
American Journal of Human Genetics
|
Abstract:
|
Mental retardation (MR) occurs in 2%-3% of the general population. Conventional karyotyping has a resolution of 5-10 million bases and detects chromosomal alterations in approximately 5% of individuals with unexplained MR. The frequency of smaller submicroscopic chromosomal alterations in these patients is unknown. Novel molecular karyotyping methods, such as array-based comparative genomic hybridization (array CGH), can detect submicroscopic chromosome alterations at a resolution of 100 kb. In this study, 100 patients with unexplained MR were analyzed using array CGH for DNA copy-number changes by use of a novel tiling-resolution genomewide microarray containing 32,447 bacterial artificial clones. Alterations were validated by fluorescence in situ hybridization and/or multiplex ligation-dependent probe amplification, and parents were tested to determine de novo occurrence. Reproducible DNA copy-number changes were present in 97% of patients. The majority of these alterations were inherited from phenotypically normal parents, which reflects normal large-scale copy-number variation. In 10% of the patients, de novo alterations considered to be clinically relevant were found: seven deletions and three duplications. These alterations varied in size from 540 kb to 12 Mb and were scattered throughout the genome. Our results indicate that the diagnostic yield of this approach in the general population of patients with MR is at least twice as high as that of standard GTG-banded karyotyping.
|