Found in Amish a genetic mutation causing mental retardation similar to Angelman syndrome
Researchers from the Research Group on Growth Factors and Cell Differentiation of the UB and the Bellvitge Biomedical Research Institute (IDIBELL) have participated in an international study, published on Journal of Medical Genetics, which has identified the genetic cause of developmental delay observed in subjects from Amish communities in the United States.
Amish are a religious community who believe in a very simple and traditional style of life. The researcher José Luis Rosa, from the Department of Physiological Sciences II and member of IDIBELL, explains that “in these communities there are high rates of inbreeding, so homozygous recessive diseases are more frequent than in general population”.
Among Amish community, researchers observed individuals who present a mental retardation similar to the one characterizing Angelman syndrome: learning disabilities, speech impairment, movement disorders and characteristic behavioral patterns of hyperactivity and concentration. “We thought that there might be a common genetic cause”, remarks Rosa. Genetic studies of fifteen individuals of Old Order Amish Community in Ohio (USA) identified a mutation in HERC2 gene, and the result is an unstable protein that does not function properly.
On the one hand, these findings will be useful to study the pathophysiology of the retardation observed among Amish community members; and on the other hand, it may be a new tool in the field of genetic counseling. According to the UB researcher, “worldwide individuals who have Angelman-like symptoms but do not show the genetic mutation associated with the disease, could have the same mutation in HERC2 gene observed in Amish; this may explain the disorder, and genetic counseling could be given to families”.
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, rescuing then cell function. However, Rosa warns that “there is still so much work to do before being able to apply a human gene therapy for this neurological disorder. This study proves for the first time the relationship between the protein HERC2 and human diseases”. Previously, this research group described the relationship between a point mutation in HERC1 gene and neurodegeneration in mice. “These studies prove an important role of HERC protein family in the pathogenesis of neuronal disorders”, concludes the researcher. Mònica Cubillos, who researches at this group of the UB and the IDIBELL, affiliated centres with the HUBc, the health campus of international excellence of the UB, has also participated in the research.
Article:
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 Medical Genetics, February 2013. DOI: 10.1136/jmedgenet-2012-101367
Researchers from the Research Group on Growth Factors and Cell Differentiation of the UB and the Bellvitge Biomedical Research Institute (IDIBELL) have participated in an international study, published on Journal of Medical Genetics, which has identified the genetic cause of developmental delay observed in subjects from Amish communities in the United States.
Amish are a religious community who believe in a very simple and traditional style of life. The researcher José Luis Rosa, from the Department of Physiological Sciences II and member of IDIBELL, explains that “in these communities there are high rates of inbreeding, so homozygous recessive diseases are more frequent than in general population”.
Among Amish community, researchers observed individuals who present a mental retardation similar to the one characterizing Angelman syndrome: learning disabilities, speech impairment, movement disorders and characteristic behavioral patterns of hyperactivity and concentration. “We thought that there might be a common genetic cause”, remarks Rosa. Genetic studies of fifteen individuals of Old Order Amish Community in Ohio (USA) identified a mutation in HERC2 gene, and the result is an unstable protein that does not function properly.
On the one hand, these findings will be useful to study the pathophysiology of the retardation observed among Amish community members; and on the other hand, it may be a new tool in the field of genetic counseling. According to the UB researcher, “worldwide individuals who have Angelman-like symptoms but do not show the genetic mutation associated with the disease, could have the same mutation in HERC2 gene observed in Amish; this may explain the disorder, and genetic counseling could be given to families”.
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, rescuing then cell function. However, Rosa warns that “there is still so much work to do before being able to apply a human gene therapy for this neurological disorder. This study proves for the first time the relationship between the protein HERC2 and human diseases”. Previously, this research group described the relationship between a point mutation in HERC1 gene and neurodegeneration in mice. “These studies prove an important role of HERC protein family in the pathogenesis of neuronal disorders”, concludes the researcher. Mònica Cubillos, who researches at this group of the UB and the IDIBELL, affiliated centres with the HUBc, the health campus of international excellence of the UB, has also participated in the research.
Article:
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 Medical Genetics, February 2013. DOI: 10.1136/jmedgenet-2012-101367