title: Screening of 20 patients with X-linked mental retardation using chromosome X-specific array-MAPH.
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 238kb. 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 7-23kb. 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 19kb region of normal copy number. The second control 50kb 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.
authors.affiliation: Department of Cytogenetics, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Kousoulidou
authors.forename: Sven
authors.initials: S
authors.lastname: Parkel
authors.forename: Olga
authors.initials: O
authors.lastname: Zilina
authors.forename: Priit
authors.initials: P
authors.lastname: Palta
authors.forename: Helen
authors.initials: H
authors.lastname: Puusepp
authors.forename: Maido
authors.initials: M
authors.lastname: Remm
authors.forename: Gillian
authors.initials: G
authors.lastname: Turner
authors.forename: Jackie
authors.initials: J
authors.lastname: Boyle
authors.forename: Hans
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: Arjan
authors.initials: A
authors.lastname: de Brouwer
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Jozef
authors.initials: J
authors.lastname: Gecz
authors.forename: Ants
authors.initials: A
authors.lastname: Kurg
authors.forename: Philippos C
authors.initials: PC
authors.lastname: Patsalis
mesh_terms: D041321:Chromosomes, Human, X / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D018628:Gene Dosage; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D046228:Microarray Analysis; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D015342:DNA Probes