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Screening of 20 patients with X-linked mental retardation using chromosome X-specific array-MAPH |
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| Authors: | Kousoulidou Ludmila Parkel Sven Zilina Olga Palta Priit Puusepp Helen Remm Maido Turner Gillian Boyle Jackie van Bokhoven Hans de Brouwer Arjan Van Esch Hilde Froyen Guy Ropers Hans-Hilger Chelly Jamel Moraine Claude Gecz Jozef Kurg Ants Patsalis Philippos C |
| Institution: | aDepartment of Cytogenetics, The Cyprus Institute of Neurology and Genetics, PO Box 23462, 1683 Nicosia, Cyprus bInstitute of Molecular and Cell Biology, University of Tartu/Estonia Biocentre, Tartu, Estonia cDepartment of Genetic Medicine, Women's and Children's Hospital and Department of Pediatrics, University of Adelaide, Adelaide, Australia dDepartment of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands eCentre for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium fHuman Genome Laboratory, Dept. Molecular and Developmental Genetics, VIB, and Dept. Human Genetics, KU Leuven, Leuven, Belgium gMax Planck Institute for Molecular Genetics, Human Molecular Genetics Department, Berlin, Germany hINSERM U129-ICGM, Faculte de Medecine Cochin, Paris, France iCentre Hospitalier Universitaire de Tours, Service de Genetique, Hospital Bretoneau, Tours, France |
| Abstract: | The rapid advancement of high-resolution DNA copy number assessment methods revealed the significant contribution of submicroscopic genetic imbalances to abnormal phenotypes, including mental retardation. In order to detect submicroscopic genetic imbalances, we have screened 20 families with X-linked mental retardation (XLMR) using a chromosome X-specific array-MAPH platform with median resolution of 238 kb. Among the 20 families, 18 were experimental, as they were not previously screened with any microarray method, and two were blind controls with known aberrations, as they were previously screened by array-CGH. This study presents the first clinical application of chromosome X-specific array-MAPH methodology. The screening of 20 affected males from 20 unrelated XLMR families resulted in the detection of an unknown deletion, spanning a region of 7–23 kb. Family studies and population screening demonstrated that the detected deletion is an unknown rare copy number variant. One of the control samples, carrying approximately 6-Mb duplication was correctly identified, moreover it was found to be interrupted by a previously unknown 19 kb region of normal copy number. The second control 50 kb deletion was not identified, as this particular region was not covered by array-MAPH probes. This study demonstrates that the chromosome X-specific array-MAPH platform is a valuable tool for screening patients with XLMR, or other X-linked disorders, and emerges the need for introducing new high-resolution screening methods for the detection of genetic imbalances. |
| Keywords: | Array-MAPH XLMR Copy number changes Copy number variations Chromosome X Patient screening |
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