Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities.
Low-copy repeats (LCRs) are genomic features that affect chromosome stability and can produce disease-associated rearrangements. We describe members of three families with deletions in 10q22.3-q23.31, a region harboring a complex set of LCRs, and demonstrate that rearrangements in this region are associated with behavioral and neurodevelopmental abnormalities, including cognitive impairment, autism, hyperactivity, and possibly psychiatric disease. Fine mapping of the deletions in members of all three families by use of a custom 10q oligonucleotide array-based comparative genomic hybridization (NimbleGen) and polymerase chain reaction-based methods demonstrated a different deletion in each family. In one proband, the deletion breakpoints are associated with DNA fragments containing noncontiguous sequences of chromosome 10, whereas, in the other two families, the breakpoints are within paralogous LCRs, removing approximately 7.2 Mb and 32 genes. Our data provide evidence that the 10q22-q23 genomic region harbors one or more genes important for cognitive and behavioral development and that recurrent deletions affecting this interval define a novel genomic disorder.
Balciuniene
Jorune
J
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Feng
Ningping
N
Iyadurai
Kelly
K
Hirsch
Betsy
B
Charnas
Lawrence
L
Bill
Brent R
BR
Easterday
Mathew C
MC
Staaf
Johan
J
Oseth
LeAnn
L
Czapansky-Beilman
Desiree
D
Avramopoulos
Dimitri
D
Thomas
George H
GH
Borg
Ake
A
Valle
David
D
Schimmenti
Lisa A
LA
Selleck
Scott B
SB
D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics*; D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid