title: Analysis of the gastrin-releasing peptide receptor gene in Italian patients with autism spectrum disorders.
abstract: 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.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Seidita
authors.forename: M
authors.initials: M
authors.lastname: Mirisola
authors.forename: R P
authors.initials: RP
authors.lastname: D'Anna
authors.forename: A
authors.initials: A
authors.lastname: Gallo
authors.forename: R T
authors.initials: RT
authors.lastname: Jensen
authors.forename: S A
authors.initials: SA
authors.lastname: Mantey
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.forename: M
authors.initials: M
authors.lastname: Falco
authors.forename: M
authors.initials: M
authors.lastname: Zingale
authors.forename: M
authors.initials: M
authors.lastname: Elia
authors.forename: L
authors.initials: L
authors.lastname: Cucina
authors.forename: V
authors.initials: V
authors.lastname: Chiavetta
authors.forename: V
authors.initials: V
authors.lastname: Romano
authors.forename: F
authors.initials: F
authors.lastname: Cali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics*; D041702:BALB 3T3 Cells; D019556:COS Cells; D016022:Case-Control Studies; D002648:Child; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D051379:Mice; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation / Q000502:physiology; D018004:Receptors, Bombesin / Q000235:genetics*
chemical_list: D018004:Receptors, Bombesin