Abstract
The short arm of chromosome 16 (16p) is enriched for segmental duplications, making it susceptible to recurrent, reciprocal rearrangements implicated in the etiology of several phenotypes, including intellectual disability, speech disorders, developmental coordination disorder, autism spectrum disorders, attention deficit hyperactivity disorders, obesity and congenital skeletal disorders. In our clinical study 73 patients were analyzed by chromosomal microarray, and results were confirmed by fluorescence in situ hybridization or polymerase chain reaction. All patients underwent detailed clinical evaluation, with special emphasis on behavioral symptoms. 16p rearrangements were identified in 10 individuals. We found six pathogenic deletions and duplications of the recurrent regions within 16p11.2: one patient had a deletion of the distal 16p11.2 region associated with obesity, while four individuals had duplications, and one patient a deletion of the proximal 16p11.2 region. The other four patients carried 16p variations as second-site genomic alterations, acting as possible modifying genetic factors. We present the phenotypic and genotypic results of our patients and discuss our findings in relation to the available literature.
Highlights
Congenital developmental anomalies and neurodevelopmental dis orders (NDDs) are frequently caused by recurrent, reciprocal micro deletions and microduplications (Deshpande and Weiss, 2018; Kaminsky et al, 2011)
The region is approximately 600 kilobase pairs (Kb) in size, located from genomic position ~29.6 to ~30.2 Mb
In close proximity lies a 95 Kb segment encompassing BOLA2 (OMIM *613183; a gene suspected to be relevant in early em bryonic development), which has undergone Homo sapiens-specific expansion relatively recently in human evolution, and has been sug gested to predispose the BP4–BP5 region to recurrent rearrangement (Nuttle et al, 2016)
Summary
Congenital developmental anomalies and neurodevelopmental dis orders (NDDs) are frequently caused by recurrent, reciprocal micro deletions and microduplications (Deshpande and Weiss, 2018; Kaminsky et al, 2011). Chro mosome 16 has one of the highest percentages [(approximately 10% of its sequence, ~7.8 megabase pairs (Mb) (Martin et al, 2004)] of SDs amongst the human chromosomes, clustered along the short arm (16p) This predisposes 16p to rearrangements, and the resultant recurrent copy number variations (CNVs) are implicated in various genomic dis orders (Cooper et al, 2011; Girirajan et al, 2012; Itsara et al, 2009; Kanduri et al, 2016; Sahoo et al, 2011; Sanders et al, 2011; Stefansson et al, 2014; Weiss et al, 2008).
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