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 ∼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.
Bibliographical noteFunding Information:
We thank all the individuals and families who participated in this study. This work was supported by the Martin Lenz Harrison Land Grant Endowment, grants from the Vikings Children’s Fund (to L.A.S. and S.B.S.), grants from the Minnesota Medical Foundation (to L.A.S.), Cancer Center support grant P30CA077598 (to B.H.), Mental Retardation/Developmental Disabilities Research Center grant HD024061 (to G.T.), and a gift from the Bigelow Foundation to the University of Minnesota Autism Center (to S.B.S.). We thank Berta Warman for expert technical assistance.