Hypo-phosphorylation of salivary peptidome as a clue to the molecular pathogenesis of autism spectrum disorders.
RP-HPLC-ESI-MS profile of naturally occurring salivary peptides of subjects with autistic spectrum disorder [ASD; N = 27:12 with diagnosis of autism, 1 with diagnosis of Asperger, 14 with diagnosis of pervasive developmental disorders not otherwise specified (PDD-NOS)] was compared to that of age-matched controls with the goal of identifying differences that could turn out to become hallmarks of at least a subgroup of ASD individuals. Phosphorylation level of four specific salivary phospho-peptides, namely statherin, histatin 1 (both, p < 0.0001) and acidic proline-rich proteins (both entire and truncated isoforms) (p < 0.005) was found significantly lower in autistic patients, with hypo-phosphorylation of at least one peptide observed in 18 ASD subjects (66%). Developmental scale assessment (Griffith or WISC-R) carried out on 14 ASD subjects highlighted a normal to borderline cognitive development in 10 of them, all included in the hypo-phosphorylated group. Phosphorylation of salivary peptides involves a Golgi casein kinase common to many organs and tissues, CNS included, whose expression seems to be synchronized during fetal development. Hypo-phosphorylation of salivary peptides suggests potential asynchronies in the phosphorylation of other secretory proteins, which could be relevant in CNS development either during embryonic development or in early infancy. These results suggest that analysis of salivary phospho-peptides might help to discriminate a considerable subgroup of ASD patients.
Istituto di Biochimica e Biochimica Clinica, Facoltà di Medicina, Università Cattolica, Rome, Italy. massimo.castagnola@icrm.cnr.it
Massimo
M
Castagnola
Irene
I
Messana
Rosanna
R
Inzitari
Chiara
C
Fanali
Tiziana
T
Cabras
Alessandra
A
Morelli
Anna Maria
AM
Pecoraro
Giovanni
G
Neri
Maria Giulia
MG
Torrioli
Fiorella
F
Gurrieri
D000293:Adolescent; D020817:Asperger Syndrome / Q000378:metabolism / Q000503:physiopathology; D001321:Autistic Disorder / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000378:metabolism / Q000503:physiopathology; D002675:Child, Preschool; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D054808:Histatins / Q000737:chemistry; D006801:Humans; D007223:Infant; D008297:Male; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D012471:Salivary Proteins and Peptides / Q000737:chemistry*
D054808:Histatins; D010455:Peptides; D012471:Salivary Proteins and Peptides