title: Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability.
abstract: Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.
authors.affiliation: University of Cambridge Department of Medical Genetics, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. css@sanger.ac.uk
authors.forename: Charles
authors.initials: C
authors.lastname: Shaw-Smith
authors.forename: Alan M
authors.initials: AM
authors.lastname: Pittman
authors.forename: Lionel
authors.initials: L
authors.lastname: Willatt
authors.forename: Howard
authors.initials: H
authors.lastname: Martin
authors.forename: Lisa
authors.initials: L
authors.lastname: Rickman
authors.forename: Susan
authors.initials: S
authors.lastname: Gribble
authors.forename: Rebecca
authors.initials: R
authors.lastname: Curley
authors.forename: Sally
authors.initials: S
authors.lastname: Cumming
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dunn
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kalaitzopoulos
authors.forename: Keith
authors.initials: K
authors.lastname: Porter
authors.forename: Elena
authors.initials: E
authors.lastname: Prigmore
authors.forename: Ana C V
authors.initials: AC
authors.lastname: Krepischi-Santos
authors.forename: Monica C
authors.initials: MC
authors.lastname: Varela
authors.forename: Celia P
authors.initials: CP
authors.lastname: Koiffmann
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.forename: Helen V
authors.initials: HV
authors.lastname: Firth
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D002886:Chromosomes, Human, Pair 17; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007859:Learning Disabilities / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D012091:Repetitive Sequences, Nucleic Acid; D016875:tau Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C054369:MAPT protein, human; D016875:tau Proteins