A New Chromosome X Exon-Specific Microarray Platform for Screening of Patients with X-Linked Disorders

Stavros Bashiardes^*, Ludmila Kousoulidou^*, Hans van Bokhoven, Hans-Hilger Ropers, Jamel Chelly, Claude Moraine^¶, Arjan P.M. de Brouwer, Hilde Van Esch^||, Guy Froyen^** and Philippos C. Patsalis^*

From the Department of Cytogenetics and Genomics, * the Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; the Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; the Max Planck Institute for Molecular Genetics, Human Molecular Genetics Department, Berlin, Germany; INSERM U129-ICGM, Faculte de Medecine Cochin, Paris, France; the Centre Hospitalier Universitaire de Tours, ^¶ Service de Genetique, Hospital Bretoneau, Tours, France; the Centre for Human Genetics, ^|| University Hospital Gasthuisberg, Leuven, Belgium; and the Human Genome Laboratory, ** Vlaams Institut voor Biotechnologie (VIB), Department of Human Genetics, Katholieke Universiteit, Leuven, Belgium

Recent studies and advances in high-density oligonucleotidearrays have shown that microdeletions and microduplicationsoccur at a high frequency in the human genome, causing variousgenetic conditions including mental retardation. Thus far littleis known about the pathways leading to this disease, and implementationof microarrays is hampered by their increasing cost and complexity,underlining the need for new diagnostic tools. The aim of thisstudy was to introduce a new targeted platform called "chromosomeX exon-specific array" and to apply this new platform to screeningof 20 families (including one blind positive control) with suspectedX-linked mental retardation, to identify new causative X-linkedmental retardation genes. The new microarray contains of 21,939oligonucleotides covering 92.9% of all exons of all genes onchromosome X. Patient screening resulted in successful identificationof the blind positive control included in the sample of 20 families,and one of the remaining 19 families was found to carry a 1.78-kilobasedeletion involving all exons of pseudogene BRAF2. The BRAF2deletion segregated in the family and was not found in 200 normalmale samples, and no copy number variations are reported inthis region. Further studies and focused investigation of X-linkeddisorders have the potential to reveal the molecular basis ofhuman genetic pathological conditions that are caused by copy-numberchanges in chromosome X genes.