Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Am J Med Genet A. 2015 Mar;167A(3):657-63. doi: 10.1002/ajmg.a.36944.


A pair of sisters was ascertained for multiple congenital defects, including marked craniofacial dysmorphisms with blepharophimosis, and severe psychomotor delay. Two novel compound heterozygous mutations in UBE3B were identified in both the sisters by exome sequencing. These mutations include c.1A>G, which predicts p.Met1?, and a c.1773delC variant, predicted to cause a frameshift at p.Phe591fs. UBE3B encodes a widely expressed protein ubiquitin ligase E3B, which, when mutated in both alleles, causes Kaufman oculocerebrofacial syndrome. We report on the thorough clinical examination of the patients and review the state of art knowledge of this disorder.

Keywords: Kaufman oculocerebrofacial syndrome; UBE3B; congenital defects; craniofacial dysmorphisms; developmental delay; ubiquitination; whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Comparative Genomic Hybridization
  • DNA Mutational Analysis
  • Exome
  • Eye Abnormalities / diagnosis*
  • Eye Abnormalities / genetics*
  • Facies
  • Female
  • Genetic Association Studies
  • Heterozygote*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Limb Deformities, Congenital / diagnosis*
  • Limb Deformities, Congenital / genetics*
  • Microcephaly / diagnosis*
  • Microcephaly / genetics*
  • Mutation*
  • Pedigree
  • Phenotype*
  • Ubiquitin-Protein Ligases / genetics*


  • UBE3B protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Kaufman oculocerebrofacial syndrome