2. Academic Validation
  3. Mutation of HERC2 causes developmental delay with Angelman-like features

Mutation of HERC2 causes developmental delay with Angelman-like features

  • J Med Genet. 2013 Feb;50(2):65-73. doi: 10.1136/jmedgenet-2012-101367.
Gaurav V Harlalka 1,  Emma L Baple,  Harold Cross,  Simone Kühnle,  Monica Cubillos-Rojas,  Konstantin Matentzoglu,  Michael A Patton,  Karin Wagner,  Roselyn Coblentz,  Debra L Ford,  Deborah J G Mackay,  Barry A Chioza,  Martin Scheffner,  Jose Luis Rosa,  Andrew H Crosby
Affiliations

Affiliation

  • 1 Centre for Human Genetics, St George's University of London, London, UK.
PMID: 23243086 DOI: 10.1136/jmedgenet-2012-101367
Abstract

Background: Deregulation of the activity of the ubiquitin Ligase E6AP (UBE3A) is well recognised to contribute to the development of Angelman syndrome (AS). The ubiquitin Ligase HERC2, encoded by the HERC2 gene is thought to be a key regulator of E6AP.

Methods and results: Using a combination of autozygosity mapping and linkage analysis, we studied an autosomal-recessive neurodevelopmental disorder with some phenotypic similarities to AS, found among the Old Order Amish. Our molecular investigation identified a mutation in HERC2 associated with the disease phenotype. We establish that the encoded mutant HERC2 protein has a reduced half-life compared with its wild-type counterpart, which is associated with a significant reduction in HERC2 levels in affected individuals.

Conclusions: Our data implicate a model in which disruption of HERC2 function relates to a reduction in E6AP activity resulting in neurodevelopmental delay, suggesting a previously unrecognised role of HERC2 in the pathogenesis of AS.

Figures