RT Journal Article SR Electronic T1 Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 332 OP 341 DO 10.1136/jmg.2009.073015 VO 47 IS 5 A1 Marwan Shinawi A1 Pengfei Liu A1 Sung-Hae L Kang A1 Joseph Shen A1 John W Belmont A1 Daryl A Scott A1 Frank J Probst A1 William J Craigen A1 Brett H Graham A1 Amber Pursley A1 Gary Clark A1 Jennifer Lee A1 Monica Proud A1 Amber Stocco A1 Diana L Rodriguez A1 Beth A Kozel A1 Steven Sparagana A1 Elizabeth R Roeder A1 Susan G McGrew A1 Thaddeus W Kurczynski A1 Leslie J Allison A1 Stephen Amato A1 Sarah Savage A1 Ankita Patel A1 Pawel Stankiewicz A1 Arthur L Beaudet A1 Sau Wai Cheung A1 James R Lupski YR 2010 UL http://jmg.bmj.com/content/47/5/332.abstract AB 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 (∼40%), behavioural problems (∼40%), congenital anomalies (∼30%), and autism (∼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.