The effect of copy number variations in chromosome 16p on body weight in patients with intellectual disability

J Hum Genet. 2019 Mar;64(3):221-231. doi: 10.1038/s10038-018-0545-5. Epub 2018 Dec 5.


Syndromic monogenic obesity is a rare and severe early-onset form of obesity. It is characterized by intellectual disability, congenital malformations, and/or dysmorphic facies. The diagnosis of patients is challenging due to the genetic heterogenicity of this condition. However, the use of microarray technology in combination with public databases has been successful on genotype-phenotype correlations, especially for body mass index (BMI) alteration. In this study, the relationship between copy number variations (CNVs) detected by microarray mapping on 16p region and BMI alterations in syndromic patients were assessed. In order to achieve this goal, 680 unrelated Spanish children with intellectual disability were included. 16p region was characterized by using microarray platforms. All detected variants were classified as: (I) one previously non-described 10-Mb duplication in 16p13.2p12.3 region considered causal of intellectual disability and severe overweight, and (II) eleven 16p11.2 CNVs of low prevalence but with recurrence in syndromic patients with severe BMI alteration (nine proximal and two distal). Proximal 16p11.2 CNVs have a dose-dependent effect: underweight in carriers of duplication and obesity in carriers of deletion. KCTD13 was identified as a possible candidate gene for BMI alteration on proximal syndromes, whereas SH2B1 gene was identified as candidate for distal syndromes. The results shown in this paper suggest that syndromic patients could constitute a reliable model to evaluate hypothalamic satiety and obesity disorders as well as generate a wide expectation for primary prevention of comorbidities. Furthermore, 16p13.2p12.3 showed to be an important region on the regulation of body fatness.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Body Mass Index
  • Body Weight / genetics*
  • Child
  • Chromosome Deletion
  • Chromosomes, Human, Pair 16*
  • Cohort Studies
  • DNA Copy Number Variations*
  • Female
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Nuclear Proteins / genetics*
  • Obesity / genetics*
  • Phenotype


  • Adaptor Proteins, Signal Transducing
  • KCTD13 protein, human
  • Nuclear Proteins
  • SH2B1 protein, human