De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive

Am J Hum Genet. 2016 Sep 1;99(3):720-727. doi: 10.1016/j.ajhg.2016.06.035. Epub 2016 Aug 18.


SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development. However, the phenotypic effects of deleterious germline variants in SON have not been clearly defined. Herein, we describe seven unrelated individuals with de novo variants in SON and propose that deleterious variants in SON are associated with a severe multisystem disorder characterized by developmental delay, persistent feeding difficulties, and congenital malformations, including brain anomalies.

MeSH terms

  • Adolescent
  • Brain / abnormalities
  • Child
  • Child, Preschool
  • Congenital Abnormalities / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Developmental Disabilities / genetics*
  • Exome / genetics
  • Failure to Thrive / genetics*
  • Female
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Minor Histocompatibility Antigens / chemistry
  • Minor Histocompatibility Antigens / genetics*
  • Pedigree
  • Sequence Deletion / genetics*
  • Young Adult


  • DNA-Binding Proteins
  • Minor Histocompatibility Antigens
  • SON protein, human