Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability.
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.
Shaw-Smith
Charles
C
University of Cambridge Department of Medical Genetics, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. css@sanger.ac.uk
Pittman
Alan M
AM
Willatt
Lionel
L
Martin
Howard
H
Rickman
Lisa
L
Gribble
Susan
S
Curley
Rebecca
R
Cumming
Sally
S
Dunn
Carolyn
C
Kalaitzopoulos
Dimitrios
D
Porter
Keith
K
Prigmore
Elena
E
Krepischi-Santos
Ana C V
AC
Varela
Monica C
MC
Koiffmann
Celia P
CP
Lees
Andrew J
AJ
Rosenberg
Carla
C
Firth
Helen V
HV
de Silva
Rohan
R
Carter
Nigel P
NP
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*
D005819:Genetic Markers; C054369:MAPT protein, human; D016875:tau Proteins