Phenotypes Associated with 16p11.2 Copy Number Gains and Losses at a Single Institution

Lab Med. 2020 Nov 2;51(6):642-648. doi: 10.1093/labmed/lmaa026.


Chromosome 16p11.2 is one of the susceptible sites for recurrent copy number variations (CNVs) due to flanking near-identical segmental duplications. Five segmental duplications, named breakpoints 1 to 5 (BP1-BP5), have been defined as recombination hotspots within 16p11.2. Common CNVs on 16p11.2 include a proximal ~593 kb between BP4 and BP5, and a distal ~220 kb between BP2 and BP3. We performed a search for patients carrying 16p11.2 CNVs, as detected using chromosome microarray (CMA), in the Molecular Diagnostic Laboratory at the University of Texas Medical Branch (UTMB), in Galveston. From March 2013 through April 2018, a total of 1200 CMA results were generated for germline testing, and 14 patients tested positive for 16p11.2 CNVs, of whom 7 had proximal deletion, 2 had distal deletion, 4 had proximal duplication, and 1 had distal duplication. Herein, we provide detailed phenotype data for these patients. Our study results show that developmental delay, abnormal body weight, behavioral problems, and hypotonia are common phenotypes associated with 16p11.2 CNVs.

Keywords: chromosome 16p11.2; chromosome microarray; copy number variation; developmental delay; genotype-phenotype correlation; phenotypic heterogeneity.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics*
  • Chromosome Duplication*
  • Chromosomes, Human, Pair 11*
  • DNA Copy Number Variations*
  • Female
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Medical Records
  • Phenotype
  • Young Adult