It is the first time that associates a mutation in HERC2 with human disease

Researchers from the research group in growth factors and cell differentiation at IDIBELL and the University of Barcelona (UB) have participated in an international study that has identified the genetic cause of developmental delay observed in Amish individuals in the USA. The research results have been published in the Journal of Medical Genetics.

Amish community
Amish is a religious community known for a simple and traditional style of life and for its reluctance to adopt modern amenities and technologies. The IDIBELL-UB researcher José Luis Rosa explains that “in these communities there are high rates of inbreeding, making homozygous recessive diseases more frequent than in the general population”.

Among the Amish community, the researchers have observed individuals with similar mental retardation observed in patients with Angelman syndrome: learning disabilities, speech impairment, movement disorders and characteristic behavioral patterns of hyperactivity and concentration. “We observed”, explains Rosa, “that there must be a common genetic cause.”

Genetic studies of fifteen Individuals of Old Order Amish Community in Ohio (USA) identified a mutation in HERC2 gene. The result is an unstable protein that does not function properly.

Genetic counseling
These findings not only will be useful to study the pathophysiology of the retardation observed among members of the Amish community, but also will be a new tool in the field of genetic counseling.

“Individuals from anywhere in the world that have similar symptoms to Angelman syndrome but do not have the genetic mutation associated with the disease and are diagnosed as Angelman-like, could have the same gene mutation in HERC 2 observed in Amish, which could provide an explanation for the disorder, and genetic counseling to their families”, explains the researcher.

Currently, the team lead by José Luis Rosa is studying how this mutation works at molecular level and they are attempting to reverse in vitro the mutation in HERC2 and rescue the cell function. Rosa warns, however, “that we are very far from being able to apply a human gene therapy for this neurological disorder”.

This study demonstrates for the first time the relationship netween the protein HERC2 and human diseases. Previously, the group of José Luis Rosa had described the relationship between a point mutation in the HERC1 gene and neurodegeneration in mice. “Overall,” says the researcher, “these studies demonstrate an important role of HERC protein family” in the pathogenesis of neuronal disorders.

Article reference
Harlalka G.V., Baple E.L., Cross H., Kühnle S., Cubillos-Rojas M.*, Matentzoglu K., Patton M.A., Wagner K., Coblentz R., Ford D.L., Mackay D.J., Chioza B.A., Scheffner M., Rosa J.L.* and Crosby A.H. “Mutation of HERC2 causes developmental delay with Angelman-like features”. Journal of MedicalGenetics (2013) Feb;50(2):65-73.

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Institut d’Investigació Biomèdica de Bellvitge