Novel mutations of ubiquitin protein ligase 3A gene in Italian patients with Angelman syndrome

Hum Mutat. 2000 Apr;15(4):387. doi: 10.1002/(SICI)1098-1004(200004)15:4<387::AID-HUMU25>3.0.CO;2-W.


Angelman syndrome is a neurobehavioral disorder caused by defects of imprinted gene(s) on chromosome 15q11-13. AS-specific DNA methylation is found in patients carrying 3-4 Mb deletions ( approximately 70%), paternal uniparental disomy (3-5%) or imprinting center mutations (2-9%), while normal methylation pattern with biparental inheritance characterizes the remaining approximately 20-25% AS patients (Stalker et al.,1998; Tsai et al.,1998). Mutations in the Ubiquitin protein ligase 3A gene (UBE3A) have been found in the latter group, but only preliminary figures are available on their frequencies. We selected a sample of 25 AS patients with a clinical diagnosis of AS and a normal methylation pattern in order to search for mutations of the UBE3A gene. Automated sequencing of exons 8, 9, 10, 11 and 12 performed on our 25 patients allowed us to identify three novel mutations: an 897insA in two unrelated familial cases, a 2544insA and an E167X in two sporadic cases. Mutation R482X previously reported in a sporadic patient was identified in a third familial case. Hum Mutat 15:387, 2000.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angelman Syndrome / enzymology*
  • Angelman Syndrome / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation / genetics*
  • Gene Frequency
  • Humans
  • Italy
  • Ligases / genetics*
  • Male
  • Microsatellite Repeats / genetics
  • Mutation, Missense / genetics*
  • Ubiquitin-Protein Ligases


  • UBE3A protein, human
  • Ubiquitin-Protein Ligases
  • Ligases