Chromosome 16p13.2 Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome on chromosome 16p13.2.

Clinical Features

Hao et al. (2015) reported 6 unrelated children with variable neurodevelopmental disorders associated with de novo heterozygous microdeletions of chromosome 16p13.2 and 1 patient with a de novo heterozygous truncating variant in the USP7 gene (602519) on chromosome 16p13.2. All had developmental delay and intellectual disability, and 5 were diagnosed with autism spectrum disorder. Additional common features included seizures (5 patients), cryptorchidism or micropenis (in 4 of 5 males), hypotonia (4 patients), and aggressive behavior (4 patients). Other features included mild nonspecific dysmorphic features and poor or absent speech with speech apraxia. Almost all patients were in special education.

Cytogenetics

Hao et al. (2015) reported 6 unrelated children with variable neurodevelopmental disorders associated with de novo heterozygous microdeletions of chromosome 16p13.2. None of the microdeletions was recurrent, and they ranged in size from 91.6 kb to 4.74 Mb. The smallest deleted region of 91.6 kb encompassed 2 genes, USP7 and CARHSP1 (616885), whereas the largest deletion encompassed 17 genes. The smallest region of overlap (SRO) extended 47.7 kb (89.7-90.2 Mb, GRCh37). The most telomeric and most centromeric breakpoints were included in the largest deleted region (chr16:4,868,744-9,611,741, GRCh37). All deletions included the USP7 gene. The patients were ascertained from microarray analysis of several large clinical databases including over 94,000 individuals.

Molecular Genetics

Associations Pending Confirmation

In a 13-year-old girl with developmental delay, hypotonia, and seizures, Hao et al. (2015) identified a de novo heterozygous truncating variant in the USP7 gene (Y143X; 602519.0001), predicted to result in haploinsufficiency. Direct functional studies of the variant and studies of patient cells were not performed. However, in vitro knockdown of USP7 in cells resulted in a decrease in TRIM27 (602165) protein levels and impaired endosomal protein recycling with decreased F-actin accumulation.