The Italian autism network (ITAN): A resource for molecular genetics and biomarker investigations

Background: A substantial genetic component accounts for Autism Spectrum Disorders (ASD) aetiology, with some rare and common genetic risk factors recently identified. Large collections of DNAs from thoroughly characterized ASD families are an essential step to confirm genetic risk factors, identify new variants and investigate genotype-phenotype correlations. The Italian Autism Network aimed at constituting a clinical database and a biorepository of samples derived from ASD subjects and first-degree relatives extensively and consistently characterized by child psychiatry centers in Italy. Methods: The study was approved by the ethical committee of the University of Verona, the coordinating site, and by the local ethical committees of each recruiting site. Certified staff was specifically trained at each site for the overall study conduct, for clinical protocol administration and handling of biological material. A centralized database was developed to collect clinical assessment and medical records from each recruiting site. Children were eligible for recruitment based on the following inclusion criteria: age 4-18 years, at least one parent or legal guardian giving voluntary written consent, meeting DSM-IV criteria for Autistic Disorder or Asperger's Disorder or Pervasive Developmental Disorder NOS. Affected individuals were assessed by full psychiatric, neurological and physical examination, evaluation with ADI-R and ADOS scales, cognitive assessment with Wechsler Intelligence Scale for Children or Preschool and Primary, Leiter International Performance Scale or Griffiths Mental Developmental Scale. Additional evaluations included language assessment, the Krug Asperger's Disorder Index, and instrumental examination such as EEG and structural MRI. DNA, RNA and plasma were collected from eligible individuals and relatives. A central laboratory was established to host the biorepository, perform DNA and RNA extraction and lymphocytes immortalisation. Discussion: The study has led to an extensive collection of biological samples associated with standardised clinical assessments from a network of expert clinicians and psychologists. Eighteen sites have received ADI/ADOS training, thirteen of which have been actively recruiting. The clinical database currently includes information on 812 individuals from 249 families, and the biorepository has samples for 98% of the subjects. This effort has generated a highly valuable resource for conducting clinical and genetic research of ASD, amenable to further expansion. Keywords: Autism Spectrum disorders; Biomarkers; Biorepository; Genetics

Analysis of RBFOX1 gene expression in lymphoblastoid cell lines of Italian discordant autism spectrum disorders sib-pairs

Several lines of evidence suggest that RBFOX1 is a key regulator of transcriptional and splicing programs in neural cells during development, and that it is expressed in a neuronal module enriched for known autism susceptibility genes. We have investigated its expression by semiquantitative RT-PCR in accessible nonbrain resources in eighteen autism spectrum disorder sib-pairs belonging to the Italian Autism Network cohort. RBFOX1 gene expression was detected in lymphoblastoid cell lines but not in lymphocytes. No significant differences between autism spectrum disorders and non-affected brothers were found. We were not able to replicate in lymphoblastoid cell lines the previously reported RBFOX1 gene downregulation in autism, even if a trend was observed. This might be due to less pronounced transcription level differences in RBFOX1 gene expression in lymphoblastoid cell lines than in brain samples. \ua9 2014 Elsevier Ltd