title: Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation.
abstract: In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere.
authors.affiliation: Department of Clinical Genetics, University Medical Centre Groningen, Antonius Deusinglaan 4, 9713 AW Groningen, The Netherlands. k.kok@medgen.umcg.nl
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Trijnie
authors.initials: T
authors.lastname: Dijkhuizen
authors.forename: Yolanthe E
authors.initials: YE
authors.lastname: Swart
authors.forename: Hanny
authors.initials: H
authors.lastname: Zorgdrager
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fehrmann
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: Klasien B J
authors.initials: KB
authors.lastname: Gerssen-Schoorl
authors.forename: Ton
authors.initials: T
authors.lastname: van Essen
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema-Raddatz
authors.forename: Charles H C M
authors.initials: CH
authors.lastname: Buys
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics; D004247:DNA / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis*; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016615:Telomere / Q000235:genetics*
chemical_list: D004247:DNA