A splice site mutation in HERC1 leads to syndromic intellectual disability with macrocephaly and facial dysmorphism: Further delineation of the phenotypic spectrum

Am J Med Genet A. 2016 Jul;170(7):1868-73. doi: 10.1002/ajmg.a.37654. Epub 2016 Apr 25.


We report on a sib pair of Indian origin presenting with intellectual disability, dysmorphism, and macrocephaly. Exome sequencing revealed a homozygous splice site HERC1 mutation in both probands. Functional analysis revealed use of an alternate splice site resulting in formation of a downstream stop codon and nonsense mediated decay. In the light of recent reports of HERC1 mutations in two families with a similar phenotypic presentation, this report reiterates the pathogenic nature and clinical consequences of HERC1 disruption. © 2016 Wiley Periodicals, Inc.

Keywords: HERC1; exome sequencing; intellectual disability; macrocephaly.

MeSH terms

  • Child
  • Child, Preschool
  • Face / physiopathology
  • Female
  • Genetic Predisposition to Disease*
  • Guanine Nucleotide Exchange Factors / genetics*
  • Homozygote
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Megalencephaly / genetics*
  • Megalencephaly / physiopathology
  • Mutation
  • Pedigree
  • Phenotype
  • RNA Splice Sites / genetics
  • Ubiquitin-Protein Ligases


  • Guanine Nucleotide Exchange Factors
  • RNA Splice Sites
  • HERC1 protein, human
  • Ubiquitin-Protein Ligases