| Autor: |
Seidita, G., Mirisola, M., DAnna, R.P., Gallo, A., Jensen, R.T., Mantey, S.A., Gonzalez, N., Falco, M., Zingale, M., Elia, M., Cucina, L., Chiavetta, V., Romano, V., Cali, F. |
| Zdroj: |
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics; September 2008, Vol. 147 Issue: 6 p807-813, 7p |
| Abstrakt: |
The gastrinreleasing peptide receptor GRPR was implicated for the first time in the pathogenesis of Autism spectrum disorders ASD by IshikawaBrush et al. IshikawaBrush et al. 1997: Hum Mol Genet 6: 1241–1250. Since this original observation, only one association study Marui et al. 2004: Brain Dev 26: 5–7 has further investigated, though unsuccessfully, the involvement of the GRPR gene in ASD. With the aim of contributing further information to this topic we have sequenced the entire coding region and the intronexon junctions of the GRPR gene in 149 Italian autistic patients. The results of this study led to the identification of four novel point mutations, two of which, that is, C6S and L181F, involve amino acid changes identified in two patients with ASD and Rett syndrome, respectively. Both the leucine at position 181 and the cysteine at position 6 are strongly conserved in vertebrates. C6S and L181F mutant proteins were expressed in COS7 and BALB3T3 cells, but they did not affect either GRPs binding affinity or its potency for stimulating phospholipase Cmediated production of inositol 1,4,5trisphosphate. In summary, our results do not provide support for a major role of the GRPR gene in ASD in the population of patients we have studied. However, there is a potential role of C6S and L181F mutations on GRPR function, and possibly in the pathogenesis of the autistic disorders in the two patients. © 2008 WileyLiss, Inc. |
| Databáze: |
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