Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders
| Autor: | Alessia Gallo, Robert T. Jensen, Mario G. Mirisola, Filippo Cali, M. Falco, Gregorio Seidita, Samuel A. Mantey, L. Cucina, Nieves González, Marinella Zingale, Rosalba D'Anna, Maurizio Elia, V. Chiavetta, Valentino Romano |
|---|---|
| Přispěvatelé: | SEIDITA, G, MIRISOLA, MG, D'ANNA, R, GALLO, A, JENSEN, RT, MANTEY, SA, GONZALEZ, N, FALCO, M, ZINGALE, M, ELIA, M, CUCINA, L, CHIAVETTA, V, ROMANO, V, CALI, F |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty BALB 3T3 Cells Adolescent DNA Mutational Analysis Population Rett syndrome Biology Mice Cellular and Molecular Neuroscience Exon Settore BIO/13 - Biologia Applicata Internal medicine Gastrin-releasing peptide Chlorocebus aethiops medicine Gastrin-releasing peptide receptor Animals Humans Point Mutation Autistic Disorder Child autism gastrin-releasing peptide receptor signal transduction G-protein-coupled receptor association study education Gene Genetics (clinical) Aged Genetics education.field_of_study Point mutation Middle Aged medicine.disease Pedigree Receptors Bombesin Developmental disorder Psychiatry and Mental health Endocrinology Italy Case-Control Studies COS Cells Female |
| Zdroj: | American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. :807-813 |
| ISSN: | 1552-4841 |
| DOI: | 10.1002/ajmg.b.30752 |
| Popis: | The gastrin-releasing peptide receptor (GRPR) was implicated for the first time in the pathogenesis of Autism spectrum disorders (ASD) by Ishikawa-Brush et al. [Ishikawa-Brush 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 intron/exon 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 COS-7 and BALB/3T3 cells, but they did not affect either GRP's binding affinity or its potency for stimulating phospholipase C-mediated production of inositol 1,4,5-trisphosphate. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text