Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Med Genet. 2010 May;47(5):332-41. doi: 10.1136/jmg.2009.073015. Epub 2009 Nov 12.

Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size.

Author information

  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, Texas 77030, USA; scheung@bcm.tmc.edu.

Abstract

BACKGROUND:

Deletion and the reciprocal duplication in 16p11.2 were recently associated with autism and developmental delay.

METHOD:

We indentified 27 deletions and 18 duplications of 16p11.2 were identified in 0.6% of all samples submitted for clinical array-CGH (comparative genomic hybridisation) analysis. Detailed molecular and phenotypic characterisations were performed on 17 deletion subjects and ten subjects with the duplication.

RESULTS:

The most common clinical manifestations in 17 deletion and 10 duplication subjects were speech/language delay and cognitive impairment. Other phenotypes in the deletion patients included motor delay (50%), seizures ( approximately 40%), behavioural problems ( approximately 40%), congenital anomalies ( approximately 30%), and autism ( approximately 20%). The phenotypes among duplication patients included motor delay (6/10), behavioural problems (especially attention deficit hyperactivity disorder (ADHD)) (6/10), congenital anomalies (5/10), and seizures (3/10). Patients with the 16p11.2 deletion had statistically significant macrocephaly (p<0.0017) and 6 of the 10 patients with the duplication had microcephaly. One subject with the deletion was asymptomatic and another with the duplication had a normal cognitive and behavioural phenotype. Genomic analyses revealed additional complexity to the 16p11.2 region with mechanistic implications. The chromosomal rearrangement was de novo in all but 2 of the 10 deletion cases in which parental studies were available. Additionally, 2 de novo cases were apparently mosaic for the deletion in the analysed blood sample. Three de novo and 2 inherited cases were observed in the 5 of 10 duplication patients where data were available.

CONCLUSIONS:

Recurrent reciprocal 16p11.2 deletion and duplication are characterised by a spectrum of primarily neurocognitive phenotypes that are subject to incomplete penetrance and variable expressivity. The autism and macrocephaly observed with deletion and ADHD and microcephaly seen in duplication patients support a diametric model of autism spectrum and psychotic spectrum behavioural phenotypes in genomic sister disorders.

PMID:
19914906
[PubMed - indexed for MEDLINE]
PMCID:
PMC3158566
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Write to the Help Desk