Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Apr;46(4):242-8.
doi: 10.1136/jmg.2008.059907. Epub 2008 Sep 19.

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders

D T Miller  1 , Y Shen, L A Weiss, J Korn, I Anselm, C Bridgemohan, G F Cox, H Dickinson, J Gentile, D J Harris, V Hegde, R Hundley, O Khwaja, S Kothare, C Luedke, R Nasir, A Poduri, K Prasad, P Raffalli, A Reinhard, S E Smith, M M Sobeih, J S Soul, J Stoler, M Takeoka, W-H Tan, J Thakuria, R Wolff, R Yusupov, J F Gusella, M J Daly, B-L Wu
Affiliations

Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders

D T Miller et al. J Med Genet. 2009 Apr.

Abstract

Background: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities.

Patients: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository.

Results: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG.

Conclusions: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
In the top panel, an ideogram of proximal chromosome 15q (15q11q14) shows the PWS/AS region and the more distal 15q13.2q13.3 region between BP4 and BP5. Lower panels show scatter plots of array CGH data for a deletion of ~1.5Mb superimposed with dye-swap scatter plot (note the mirrored distribution of spots). The lower scatter plot represents a duplication of ~500Kb within the BP4–BP5 interval. The relative positions of 7 genes (6 reference genes and one miRNA gene) are shown in the bottom panel (grey bars). The 1.5Mb deletions (chr15:28.719–30.232Mb; hg18) include all 7 genes, while the 500 kb duplications (chr15:28.902–29.404 Mb; hg18) contain 4 genes (MTMR15, MTMR10, TRPM1 and hsa-mir-211) within the BP4–BP5 at chromosome 15q13.2q13.3.
FIGURE 2
FIGURE 2
Photographs of five patients with 15q13.2q13.3 BP4–BP5 microdeletion, and two patients with BP4–BP5 microduplication, all from the CHB cohort (numbering corresponds to Patient Number in the text and Supplemental Data). We obtained written consent to publish photographs for each individual included in this figure.
See this image and copyright information in PMC

References

    1. Shaw-Smith C, Redon R, Rickman L, et al. Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J Med Genet. 2004;41(4):241–8. - PMC - PubMed
    1. Schoumans J, Ruivenkamp C, Holmberg E, et al. Detection of chromosomal imbalances in children with idiopathic mental retardation by array based comparative genomic hybridisation (array-CGH) J Med Genet. 2005;42(9):699–705. - PMC - PubMed
    1. Lupski JR. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 1998;14(10):417–22. - PubMed
    1. Koolen DA, Vissers LE, Pfundt R, et al. A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Nat Genet. 2006;38(9):999–1001. - PubMed
    1. Sharp AJ, Hansen S, Selzer RR, et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nat Genet. 2006;38(9):1038–42. - PubMed

Publication types